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1:14:08 PM JANET WOODCOCK, FDA: Now we’ve already started taking the necessary steps to move this proposal forward. I’m spearheading an implementation and change management group that’s focused on developing detailed plans to ensure the successful execution of this program. We look forward to sharing further details next month, and in the future, on our progress as we initiate this agency’s proposals in close coordination with internal and external stakeholders, while also ensuring we meet our labor obligations.
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1:17:32 PM ROBERT CALIFF, FDA: Well, we’re really working on that now, and we don’t have anything new to say today. But you’re well aware, I think, probably based on your question, that we’ve got new authorities on cosmetics, which we had sought for a long time to help that industry produce the highest quality product. And so now we have to figure out exactly where in the system it will fit.
I still love Dr. Woodcock’s quote from one of the discussions we were having yesterday. I think 100% of people do agree that cosmetics are not food. So we need to find the right home and we’re working on it under the guidance of our new chief science officer, Dr. Bumpus, who just joined us from Hopkins. Dietary supplements is a whole different kettle of fish that we can discuss at a later time, but I assure you will be working on that.
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1:22:06 PM QUESTION: I’m wondering if any of the proposed plans and restructuring include the reassignment or firing of anyone who was involved in the FDA breakdowns around infant formula. And if not, I’m just wondering if we should expect in the coming months, anyone to be either reassigned or fired.
1:22:37 PM ROBERT CALIFF, FDA: I’m surprised by the way that question was asked, but I guess you have the right to ask it. We are– in the reconfiguration that we’re doing, no one’s going to lose a job because there’s a lot more work to do than the number of people that we have. We’ve already made changes in leadership, as you know, as things evolve in a program. But the short answer is no one’s going to be reassigned or fired because of the infant formula situation.
1:23:20 PM JANET WOODCOCK, FDA: We issued a complete report on that. And that was a systems problem, not an individual problem. And so the system fixes that we are putting in place, both the information technology support as well as many of the changes, will address all the different issues from consumer complaints. We do not have, right now, a front end for consumers, a single front end to come through. We are addressing that and so forth all down the line. So– but I wouldn’t say– we are not considering, after we looked into that carefully, an individual failure. This was a failure of the systems that we had, to the extent there was a failure, to provide the information to the right people at the right time.
1:24:17 PM ROBERT CALIFF, FDA: And I would just– one last comment on this, where there could have been better performance, that’s reflected in the performance evaluation system, that employee– and of course, that’s confidential information between supervisors and employees.
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1:27:01 PM ROBERT CALIFF, FDA: One press article quoted me as saying, what I did say, which is that we are looking for a barking cat here. We’re looking for an unusual person who can really deal with the complexity of the foods enterprise spanning all the way from human nutrition to infant formula all the way up to bacteria and safety on the farm and everything in between. This person is also going to need to be a leader because change is hard in any circumstance and we have a lot of great people, but there’ll be a lot of work to make the changes, and this person will have to have a feel for the operational issues that are involved.
But I can already tell you, as you might imagine, I’ve been talking with a lot of people over the last three months, and there are highly qualified people who would be interested in the job. And if you know of anybody, let us know. Jobs will be open very shortly, including other executive jobs in the system.
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1:34:40 PM JANET WOODCOCK, FDA: Well, efficiencies, for example– and we’re going to do these changes across the board, not just with the foods program, vis a vis ORA. The particular difference in, for ORA and foods, is in the state partnership area. But as far as inspections and investigations and so on, this will be across the board with all the programs. For the last year, for example, we’ve transitioned– we’re building a workflow management system that will join the centers for the first time in ORA so that they’ll be calling, ordering inspections, carrying out the inspections, and then eventually dealing with the back end of the inspections, potential compliance actions and so forth, on the same platform. Right now, they’re siloed. And so there’s like 11 different ways that centers can order inspections to ORA through SharePoint or emails and so forth, Excel spreadsheets. So we are modernizing that infrastructure.
And at the same time then, we will change the business rules about how that all works, how the planning for inspection goes, how the compliance function is carried out, but it’ll be brought together by IT that join those, all those programs. So that’s one example. We’re also building a centralized inventory of all establishments, pulling together all the different inventories that reside all over the agency, and making it a single source of truth. Here’s a facility, it makes these products owned by this company, which has these other establishments and so on. So we’re trying to build a modern system that will bring everyone together. So that’s just one example. But yes, it will go across all the different programs. So the ORA is dealing with a unified system of interaction with its customers.
MIKAEL DOLSTEN, PFIZER [00:43:24]
I think it actually offers an opportunity when you have the breadth to have a pipeline with different platforms. We think that the COVID flu, which contains six components, and we have made a real good progress in enrolling the study and will start to share our data in the near future, but by itself, of course, a fast track forward pending data, but for the use of a potential triple vaccine, rather than adding up more and more mRNA with the current technology, that we have seen can lead to reactogenicity limitation and less tolerability, we think this flexibility to add on a protein may give you the perfect balance between efficacy and tolerability.
ALBERT BOURLA, PFIZER [00:44:15]
Thank you, Mikael. And also, as you know, we are mastering multiple technologies in vaccines, so we are using fit for purpose here. Every time we feel that the technology appropriate for the problem we’re trying to solve, we apply this technology. Flu and COVID, they are speed is of essence, because there are variants that are coming. So mRNA is ideal position to address this challenge. With RSV, the virus is not changing that often. So a protein approach that has a premium tolerability profile, almost like placebo was when we saw the data, the responses of the vaccine arm compared to the placebo arm were very difficult to separate with very, very high efficacy, in our case. I think it’s the best way to move forward. It has the benefit of having multiple approaches and multiple technologies.
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ALBERT BOURLA, PFIZER [01:21:39]
If there is an end of emergency, we don’t think that will have any impact on current EUAs. It will have an impact on issuing new EUAs. But I don’t think that anything changes in the way that, emergency or not, whether inventories will be managed or the access that patients will have in any of these treatments.
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QUESTION [01:24:02]
And then just on the flu COVID combo, if we assume you have positive flu phase three data in the second half of the year, positive phase one, combo data in the first half, would you expect to move a combo into phase three? Or is there a possibility you will not need a a full phase three combo study to proceed to filing an approval?
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MIKAEL DOLSTEN, PFIZER [01:25:08]
We expect that you need a phase three that is based on immunogenicity and safety, and not a large long trial based on events. So we think we can complete that fast. And if anyone can do it first, it’s we. So that’s very high on our list. Currently pending data to move with lightspeed in.
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QUESTION [01:26:11]
Following commercial approval, the withdrawal of the EUA, will pharmacist’s prescribing remain intact?
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ALBERT BOURLA, PFIZER [01:26:50]
And the first one is, I don’t know, on the– if the the pharmacists will– it’s very unlikely, I think, but I don’t know. We don’t have it in our assumptions right now.
DR. HUGH AUCHINCLOSS, NIH [00:00:14]
We’re meeting virtually today as we plan to do every January council, regardless of COVID status. I would be very pleased if, when it comes to May, if a new permanent director could make the decision then about whether we meet in person.
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DR. HUGH AUCHINCLOSS, NIH[00:05:52]
Now you should know that there is a global search underway to find a replacement for Dr. Fauci as the institute director. The announcement went out on November 16th. The closing date was theoretically January 17th, but in fact, applications will be accepted until the position is filled. But January 17th was the time at which the search committee can begin reviewing the applications and is beginning to do interviews. So the process is underway.
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DR. HUGH AUCHINCLOSS, NIH [00:09:03]
Now, I mentioned Greg Folkers earlier, and this is a picture of him. As I say, he worked directly for Dr. Fauci for 25 years. And Laurie Doepel also was in federal service for over 30 years and is a gifted editor and writer who has been working with Dr. Fauci for many years now on the scripts of many of his remarks and some of his papers.
The two of them have both agreed to come back as contractors, partly working for NIAID, but probably spending more of their time actually working still for Dr. Fauci in his private capacity.
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DR. HUGH AUCHINCLOSS, NIH [00:31:26]
So clearly there need to be innovative approaches to induce broad durable protection against coronaviruses, not only those we know, but we don’t know yet, which leads to our effort to develop next generation vaccines.
Our first main effort is to develop a pan coronavirus vaccine. And in 2021, we actually went ahead and awarded seven awards to centers to develop a pan coronavirus vaccine. And at least one of those centers we expect to begin clinical trials in the very near future.
The other area of major interest is mucosal vaccines, with the aim of preventing infection, not just severe disease, so that we can block the transmission of this virus that seems so transmissible. This is not necessarily going to be as easy.
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DR. HUGH AUCHINCLOSS, NIH [00:33:43]
There are candidate mucosal vaccines that are moving towards clinical trials, some of– all of which, I believe, have been supported in part by NIAID. This one from St Louis and this one from our own intramural program.
But we have worked hard to stress to the funding agencies downtown that this is not going to be a repeat of Operation Warp Speed, where we have success in a less than one year time. This is a longer term effort that we are undertaking.
10:58:52 AM QUESTION: Just have a one quick question, so if you have had vaginal sex with a new partner, in the last three months, you are eligible to donate? But if you have had anal sex with new partner in the last three months, you are not eligible? Is that a correct interpretation of the new guidance?
10:59:22 AM PETER MARKS, FDA: That is a correct interpretation and that has to do with the risk of exchanging blood that goes with vaginal intercourse versus anal intercourse, whether it’s a man or a woman. It’s gender inclusive, essentially, because anal sex is associated with a higher risk of exchange of blood.
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11:01:13 AM PETER MARKS, FDA: So this is simply a matter of following the data that we have at this time, which is that we know that people who take PrEP, at least at this point with our knowledge of PrEP, that if you look at the population overall taking PrEP, there’s a certain risk currently of contracting HIV. It’s about 1 in 100 person years with current PrEP regimens, about 1 in 100 or 0.5 in 100 depending on which PrEP regimen. And so that’s for all comers.
So until we can better sort out, who is of lower risk in that in that group taking PrEP, we need to put this this donor deferral in place for PrEP. That’s not to say that we won’t continue to look at this and try to refine things further. It’s just that, ultimately, as we move forward, we have to maintain the current safety of the blood supply.
And moving forward, as we’re doing now, this may not be the final resting place of where we end up, but it allows us to move forward and to at least make a leap forward to allow some men who are not taking PrEP to donate.
And the ADVANCE study, by the way, showed that there is a significant fraction of men who have sex only with one partner who should be able to donate.
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11:03:31 AM PETER MARKS, FDA: So, there are certain things that we have to do right now, from practical perspectives. In our blood donor rooms, it gets very complicated if we have to worry about insertive and receptive anal sex. At some point, we may be able to get there, but right now, I think again this is a first step in the right direction.
And I think trying to sort out the risks here, and trying to make sure that we don’t increase risk by having things clear, will be challenging. This is a great first step, I think, in getting in the right direction.
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11:04:56 AM QUESTION: Thanks for taking my question. Sort of following on the previous two questions, what is the data that prevents you from considering narrower criteria, like heterosexual couples or protected sex? Why were those things that you couldn’t caveat here?
11:04:56 AM PETER MARKS, FDA: So thanks. Great question.
Unfortunately, condom use is something that is, A, less than perfect, but even when used properly, unfortunately, because of the nature of anal intercourse, the condom failure rate is about one percent– one to two percent in some studies. And so protected intercourse is, at least at this point in time, from what we have in terms of data, it does not meet the standards for what will help us feel comfortable that we’re preventing the risk of transmission. So that’s the issue there.
We’ve tried to look at the various permutations of what we could do, and that’s what the ADVANCE study did, and at this point the simplest thing that we could implement, which has been implemented in Canada and the United Kingdom, so this policy now is fully consistent with the deferrals in Canada and England. In England and in Canada, I think the deferral for PrEP use is a month longer, or four months, but regardless, we’re very consistent now with other countries who have moved forward and advanced their policies.
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11:11:44 AM PETER MARKS, FDA: Thanks so much for that question. So, there is obviously, once these are draft recommendations, once they go final, they will need to be implemented in the donor history questionnaire, which in many places is an electronic questionnaire.
So we are hoping, as we go through this comment period, to work with the blood collectors to get them primed to start making the modifications necessary to move to this individual risk assessment. And we’ve already started that outreach and we’ve had very good receptivity.
I think the the blood collectors, the major blood collectors, many of them were involved in the ADVANCE study, and so they are ready and waiting to start to be ready to make these changes.
I would not anticipate the same type of delay that we saw after our change from the indefinite to the 12 months deferral, which took some time in some cases with this change. I hope there is a very minimal, if any, delay from when the guidance goes final to when people are able to donate.
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11:14:01 AM PETER MARKS, FDA: So I’d like this– I’d like it to send the message that we are moving now to an inclusive policy for blood donation that is as inclusive as it can be. That we will continue to work to try to make sure that we have policies that allow everyone who wants to donate blood to be able to donate blood, within what the science allows, to make sure that the blood supply remains safe.
And so I think this is a really a significant step forward. It puts us in line with the other countries in the world that have moved to the most inclusive policies that could be supported by the available science.
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11:14:55 AM ROBERT CALIFF, FDA: And I’d just add that donating blood is one of several really important symbolic methods of demonstrating one’s caring for other people. So we want to make that available to everyone possible, in the context of a safe blood supply, since as we all know, blood is life-saving and essential and almost all of us will need blood products at one time or another as we go through life.
8:54:39 AM DAVID KASLOW, FDA: It is an honor to join the 178th meeting of VRBPAC for the first time as director of OVRR. And as Dr. Marks noted, this is a consequential meeting to determine if we’ve reached a point in the pandemic that allows for simplifying the use of current COVID 19 vaccines, and if it is the moment to implement a more routine approach to periodically updating the strain composition of these vaccines.
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9:00:44 AM DAVID KASLOW, FDA: Most of the general U.S. population have been sufficiently exposed to spike protein, either to infection, vaccination or both, such that a single dose of a COVID-19 vaccine would induce or restore vaccine effectiveness. As you will see, some preliminary age based data that suggest which age groups might fit into this category.
As with the influenza immunization schedule, it is also possible that some risk based adjustments to the immunization schedule may be necessary. It could be that more than one dose is needed for high risk older adults, persons with compromised immunity, and young children who have not yet been completely immunized.
At this time, those risk based adjustments remain to be determined. Next slide.
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9:20:24 AM HEATHER SCOBIE, CDC: This is seroprevalence data reflecting categories of vaccine and infection history among U.S. adult blood donors overall on the left, and by age group on the right, for two surveys conducted in the first and second quarters of 2022.
As expected, increasing proportions of vaccine induced immunity only, in blue, and both vaccine and infection induced immunity, in green, were observed in older age groups, while higher proportions of infection induced immunity only, in yellow, were observed in younger adult age groups.
During the second quarter survey, as shown in slightly darker shades, proportions of adults with both infection vaccine and infection induced immunity increased across all age groups. I note that the most recent data presented here are for June 2022. Next slide.
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9:21:37 AM HEATHER SCOBIE, CDC: This is pediatrics seroprevalence data from a national survey of commercial laboratory specimens by age group from March to December 2022, including new unpublished data.
On the left is infection induced seroprevalence, which was noticeably lower for children ages 6 to 11 months in light blue, and children ages 12 to 23 months in green, than in older age groups. On the right is combined seroprevalence for infection and vaccine induced immunity, which was higher overall.
However, combined seroprevalence was still lower for infants just 6 to 11 months and children ages 12 to 23 months. Next slide.
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9:27:54 AM HEATHER SCOBIE, CDC: One, in terms of the regional variation, those graphs can be viewed by– or charts with the maps can be viewed by week, if you’re interested in regional variation, on the COVID– CDC’s COVID data tracker.
But early on, before Delta became the predominant circulating lineage, we did observe regional circulation of a few lineages, but never kind of reached predominance in the United States. An example maybe like Epsilon, which was circulating on the West Coast. But since then, what we observed is that if a variant has some sort of advantage, that it’s generally taken over and swept across the country no matter where it’s first detected.
And I think there’s reasonable suspicion that that will probably occur with XBB.1.5 as well. So it’s more or less just a matter of time, but I guess time will tell.
We’re in, of course, a new era with variants, with this so-called variant soup. We don’t have a great term for it, but it’s a collection of BA.5 and BA.4 and BA.2 related lineages. And as I noted, they often just differ by one or two amino acids from each other, which has been one reason where we where we haven’t for a while had a clear kind of winner in terms of selective advantage.
But it’s seeming like, with XBB.1.5, we’re at that place now.
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9:30:40 AM HEATHER SCOBIE, CDC: Home test results are definitely not incorporated into genomic surveillance at this point. There’s no framework for testing those home test specimens for sequencing.
There are efforts to make like Make My Test Count, which is an effort by– a government effort where you can report your home test results, and there are– there’s a website, and I believe you can see the results through that website. And CDC is working to make that– those data available publicly.
I know that’s either imminent or has already posted.
But that’s a separate issue in terms of making those data available, as part of surveillance and validating whether they work as a surveillance measure that we can follow over time. But you’re right in that in pointing out that that framework isn’t included in terms of what we have currently for genomic sequencing, which is limited to swabs.
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9:32:08 AM HEATHER SCOBIE, CDC: Well, if you’re worried– people who do home tests in general are not– they’re either before the point of care seeking or they have less severe cases, or they’re doing asymptomatic screening for whatever reason because of contact. So if we were worried about catching all of those people and what’s circulating among those more mild cases, I would say we have a problem.
But I guess I don’t think that that’s a problem that we’re only focused on swabs, which are generally for people either seeking care because of more severe illness or because they need to confirm that their – the test they ran at home is correct.
So I don’t think that it’s a problem that we’re not catching them in genomic surveillance.
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9:51:31 AM RUTH LINK-GELLES, CDC: Additionally, we have not seen substantial evidence of waning so far, but only had stable estimates three months after receipt of the bivalent dose due to case counts and timing of vaccine authorization.
And so we’ll continue to monitor potential waning throughout the spring. Next slide.
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10:16:40 AM NICOLA KLEIN, VACCINE SAFETY DATALINK: So here is a summary of the findings of ischemic stroke following bivalent Pfizer COVID 19 mRNA booster vaccination in persons aged 65 or older.
So we have a statistical signal that has persisted for seven weeks. I will say that data from just a couple of days ago, it has attenuated substantially, and actually did not take that signal. This past week, for the first time, the rate ratio had slowly attenuated from 1.92 to 1.47. This continued to be seen until just a couple of days ago.
Additional signal investigation analysis, we found temporal clustering evaluation of a significant cluster left at 22 days after vaccination. Supplemental analyses using unboosted concurrent comparators show rate ratio of 1.07. That’s not statistically significant.
In a small subset of charts reviewed, most confirmed cases had coadministered high dose or adjuvanted flu vaccine. Analyses evaluating a high dose or adjuvanted flu vaccine showed a rate ratio of two that was significant. A separate analysis, which are not shown here, did not detect an elevated rate ratio for stroke after (inaudible) data not shown.
And then finally, excuse me, can you go back one more? – a supplemental analysis suggests comparison interval of 22 to 42 day rates were lower than expected. Next slide.
So there are some additional considerations to think about with these data. So there are small numbers of strokes, imprecise rate ratios, which limits analyses. We had reduced follow up time after Moderna boosters, due to distribution delays, and concomitant flu analyses were limited by small numbers.
It’s difficult to interpret the temporal clustering during risk and comparison intervals. There’s also possible unmeasured confounding. Results may have been influenced by confounders that vary over time. And importantly, do early adopters of bivalent booster vaccines have a greater risk of cardiovascular events? However, the same trend has not been observed for acute myocardial infarctions. And it’s difficult to– it’s very challenging to assess the potential impacts of differential vaccine availability after the EUAs, there being so much more Pfizer and Moderna being available, and then the possible roles of SARS-CoV-2 infection before the booster dose.
The background incidence of SARS-CoV-2 infection was rapidly changing during bivalent booster uptake and just to– a word on analysis that we did, which excluded cases of the COVID 19 diagnosis or positive test for the prior 30 days. So that was our case definition. However, asymptomatic infections and antigen tests are not consistently documented in our EHR, which is not unique to VSD, but that is what’s happened in the landscape of COVID.
However, when we did chart reviews, we did not find recent SARS-CoV-2 infection exposure evidence. Next slide.
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10:20:40 AM TOM SHIMABUKURO, CDC: So to sum up, we’ll continue to monitor weekly and explore potential data related explanations for the statistical signal in VSD. We’ll consider expanding chart reviews to all VSD sites, and we’ll consult with other surveillance systems to better understand the possible role of concomitant high dose or adjuvanted flu vaccination with COVID 19 vaccination, and the possible decreased rate of stroke in the 3 to 6 weeks following vaccination. Next slide.
Just want to reinforce that CDC continues to recommend that everyone eligible for a COVID 19 mRNA bivalent booster or a flu vaccine get vaccinated. And CDC and FDA are engaged in epidemiologic analysis regarding co-administration of COVID 19 mRNA bivalent booster and flu vaccines.
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10:27:35 AM TOM SHIMABUKURO, CDC: And I think that fairly shortly there will be an opportunity to present these findings, in the context of a benefit risk assessment at an ACIP meeting.
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10:39:12 AM RICHARD FORSHEE, FDA: Because of the results that have been presented from the CDC and VSD analyses, we have done further exploration as to– into other datasets, looking for information on the potential safety risk of ischemic stroke.
So far, the data that we have seen suggest the absence of a safety risk for the bivalent boosters in age 65 years and older. There have been no excess reports of stroke from VAERS. I’ve just reported on what we found in our CMS sequential analysis, showing no increased risk of stroke. The Veterans Affairs database has also done a preliminary run, and did not find an increase in stroke. We contacted a number of our international regulatory or regulatory agencies and various countries in Europe, as well as Israel, who have indicated no increased risk of stroke in their surveillance systems. We also contacted Pfizer and they consulted their global safety database and they did not see any increase or signal for the ischemic stroke in their systems.
In any case, because of the information that we have seen, we at FDA have launched a formal epidemiological study, and we’re working on the protocol right now, to study, in particular, the concomitant administration of a high dose or adjuvanted influenza vaccines, and the COVID 19 bivalent vaccine, in order to prepare for this potential vaccine co-administration in the 2023-2024 season.
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11:17:13 AM JOHN BEIGEL, NIH: Without a doubt. And just to bring it back, you can see at the very bottom, and I didn’t highlight it and we started in March and at that time we had the BA.1. So that was how we constructed the trial. And we did add a stage four, which is wildtype BA.1 versus wildtype BA.4/5.
We’re just starting to get that data and that the n that we had was really small, so we chose actually not to present that, because I think that’s way too speculative at this juncture.
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11:53:33 AM DARIN EDWARDS, MODERNA: Moderna continuously monitors four emerging variants and classifies variants based on the incorporation of immune evading mutations and on the measured growth dynamics of these emerging variants. For those that meet our pre-specified criteria, preclinical mRNA materials are prepared and key manufacturing steps are initiated as soon as possible to prepare for the possibility of vaccine update requests from health agencies.
An example of this process is our preparation for three currently circulating variants, which we began in early fall of 2022. These efforts are performed to allow for expedited delivery of new vaccines, should they be requested.
An example of the benefits of this ongoing effort was seen in Moderna’s rapid development of the BA.4/5 booster vaccine. The BA.4/5 booster bivalent vaccine preparation had begun in spring 2022, based on our epidemiological monitoring and variant risk assessment efforts. Subsequent to the FDA’s request for a BA.4/5 bivalent vaccine in June of 2022, pre-clinical evaluations were completed and large scale manufacturing batches were prepared.
This rapid development and evaluation enabled authorization in late August and initial vaccine supply was subsequently released. This also highlights Moderna’s preparation for an annual vaccine selection process and our ability to respond quickly for an off cycle update, should an immune evading variant emerge.
Moderna’s ongoing monitoring and variant response effort has enabled the development and evaluation of more than 19 monovalent and bivalent vaccine compositions. In addition, through our real time monitoring efforts, we have started our development and evaluation process for three recently emerged variants: XBB.1, BQ.1.1, and BN.1.
In our preclinical evaluation of these new variant vaccines, we’re not only assessing monovalent and bivalent vaccines, but also novel bivalent combinations. Those that include the original strain, and also those that do not. These novel bivalent compositions are listed.
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12:02:03 PM RITUPARNA DAS, MODERNA: Yes, and I can– we can bring up the slide for the the immunogenicity of the monovalent BA.1 vaccine arm as well as the bivalent arm. And this is all in the preprint that was posted yesterday. But you see the– so on the– on the left part of the slide is the monovalent, the purple is that BA.1 only. And on the right side of the slide is the BA.1 bivalent, and you see those geometric mean titer ratios on the bottom. And so they each have an individual– they are each randomized to their respective original vaccine.
And so you see the geometric mean titer ratios on the bottom are very similar, 1.7 and 1.5. But if you look at the– well, yes, here we go. But if you look at the original strain data here, the responses to the ancestral strain, you do see that there seems to be some benefit for the bivalent vaccine there. The geometric mean ratio is 0.8 versus 1.0.
Now, whether this– in our other studies, we have shown that using a bivalent, you can perhaps diversify the immune response that you get in order to kind of try to prepare or be closer to the ongoing evolution. And perhaps this gets at that benefit for the bivalent.
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12:28:09 PM KENA SWANSON, PFIZER: For the second question on two versus three doses, so the ongoing pediatric study evaluating the primary series is evaluating what– we will have data generated after the second dose, as well as three doses of the bivalent vaccine.
And knowing that as the variants change, it’s a moving target, and the current dose level for the original vaccine in the pediatric population is three micrograms, but we also want to understand as you’re changing these vaccines, do they perform the same way?
So there is also a dose ranging component within that primary series portion of the pediatric study.
HAYLEY GANS, VRBPAC: And it includes higher doses?
KENA SWANSON, PFIZER: Yes.
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12:30:41 PM BILL FALSTITCH, PFIZER: On the first question, could the 100 day timeline be similar if we had, let’s say, more than two components to the vaccine? Yes, it could be. We have the production capability to enable that, in a similar roughly 100 day timeline.
And then as to the second portion of the question, if the U.S. makes a decision in June, would that bind the world to a similar decision? (crosstalk) answer is not not necessarily, so as Dr. Swanson mentioned, this past year we we delivered BA.4/5 bivalent to the U.S., we delivered (crosstalk) a BA.1 bivalent elsewhere in the world. It was on separate decision cycles, and we were able to manage that with no concerns and fulfill all the global demand. So we could be flexible like that again if we needed to.
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1:02:04 PM BRUCE GELLIN, VRBPAC: Just to clarify about the timing of production, you are asking for end of first quarter decision for a six month production, is that right?
FILIP DUBOVSKY, NOVAVAX: That’s right. I think very much like you see with other complex biologicals, that’s the time frame that required for us to bring adequate vaccine to the market.
Now, a couple of points. I’d also ask for the ability to antigenically match strain, and that could certainly accelerate our time frame. And then just like the other sponsors, we make these things all the time, and if something new comes up, crops up, we start manufacturing.
So depending on how far we are along that manufacturing process, that time frame could be shortened. But if you give us a strain we haven’t worked on, it is a six month time period from providing that sequence to delivering product.
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2:47:55 PM JERRY WEIR, FDA: Now, there were several reasons why in June we did not consider and we collectively, the FDA and the VRBPAC, did not consider the recommendation for a bivalent vaccine for the primary series. One reason was, of course, there was very little data to help us decide whether it was applicable for a primary series. There was nothing at the time that we– that we could turn to.
There was also some data at that time that made us wonder whether– that was in the literature that suggested that Omicron might not be as immunogenic as earlier strains, and therefore not lead to as good of a cross-reactive antibody response as earlier strains.
Now we know a lot more, and it turns out that’s probably not that important because that crossreactivity to earlier strains, well those earlier strains simply don’t exist. And it doesn’t seem to hold true for later derivatives of Omicron.
And finally, there was probably a consensus to move conservatively at that time in June, and the WHO had not recommend it changing the primary series. And I think the committee felt more comfortable taking a conservative approach and making the recommendation only for booster strains.
But we know a lot more now, as I’ve already said, right now, we’ve we’ve evaluated these booster vaccines containing these bivalent vaccines, and the available immunogenicity and effective date effectiveness data support the use of these COVID 19 vaccines, bivalent vaccines, for booster vaccination. I think the data is pretty clear.
We also have now recent preclinical and clinical data that indicate the use of bivalent vaccines will improve the antibody responses against Omicron variants when used in either naive animals or as a primary series vaccine in young children, respectively.
I’ve listed the first two references, listed are preclinical studies from Moderna and Pfizer, BA.4 and BA.5 bivalent vaccines in naive animals. These have been come out in print in the last few months. And then you heard earlier today Moderna’s data for a study of a bivalent vaccine containing a BA.1 component when used as primary series of vaccine in young children.
So I think the data is pretty reassuring and support this alignment of a primary series and booster vaccine composition.
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2:52:28 PM JERRY WEIR, FDA: We recognize that additional data needed to pursue a simplified periodic vaccination strategy may be needed. It may include a better understanding of age based rates of virus exposure and vaccination and identification of risk groups that would benefit from an alternate immunization strategy.
One example of a proposed simplification of vaccination strategy is shown in this slide, and we can use this as a starting point for discussion, which we will get to in a few minutes.
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2:54:57 PM JERRY WEIR, FDA: A tentative framework for addressing future COVID 19 vaccine strain composition was proposed back in April. The committee had a vigorous discussion about this.
Since that time, and since our June meeting, manufacturers have requested additional details and clarity about the process for updating the strain composition of COVID 19 vaccines.
Specifically, they have asked about timing, process, and methodology for making a strain composition recommendation, and the data package needed for manufacturers for authorization or licensure.
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2:56:31 PM JERRY WEIR, FDA: We threw this out as a placeholder, as a possibility for sometime in the late spring. The goal of that meeting, of course, would be to review the current situation, to reassess where we are with current vaccines, how well they’re covering, how well they’re doing, and decide if improvement is needed at all for benefit of the object.
Of course, before anyone says anything, the goal is not to chase variants. None of us think that’s that realistic. But I think our experience so far with the bivalent vaccines that we have do indicate that we can continue to make improvements to the vaccine. And that would be the goal of these meetings is to get together, ask ourselves can we make improvement and decide what is feasible?
Of course, the emergence of a more pathogenic escape virus in the context of a public health emergency would prompt an ad hoc meeting of the VRBPAC. We have done that previously for influenza, for example, in the 2009 pandemic, if that were to happen again, I think we’ve shown that we can be flexible and we would be prepared to respond as needed if something like that happened.
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3:06:28 PM JERRY WEIR, FDA: I can give you an opinion, but that’s all. First of all, I think this is exactly the sort of thing that we would discuss at the next VRBPAC where we talk about a strain composition.
I think it would be a debate worth having. In fact, it’ll probably be needed. We will need to have it of whether we should continue something like a bivalent vaccine containing a strain that hasn’t existed in three years, versus trying to tailor it more. I don’t know the answer.
My gut feeling, which– I mean, my gut doesn’t produce the data, but my gut feeling is that a monovalent would have been a little better now than the bivalent, but I think there were reasons why we chose the bivalent, which were pretty good at the time.
But to answer the real question, where are we headed? I don’t know.
I think we evaluate the data, what we have at the time, we feel like we need to make a new recommendation, and we make the best choice that we can. If that’s a bivalent, maybe that’s what we do. If it’s a monovalent, that’s what we do. But I think we just follow the data we have.
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3:09:32 PM ARCHANA CHATTERJEE, VRBPAC: So the first one is actually pretty simple, which is, Dr. Weir you talked about the different manufacturers and the timelines and all of that, and them updating the vaccines. What if a manufacturer decided not to update its vaccine? Would the FDA then withdraw the EUA or licensure of that particular product that they were using, or has that– is that not a topic that has been discussed so far?
3:10:12 PM JERRY WEIR, FDA: Oh, it’s probably not a topic that I can give you a definitive answer on today. It’s not one that we haven’t thought about. I– we would have to have a serious internal discussion about how to approach that.
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3:35:43 PM PETER MARKS, FDA: We’re starting to see some seasonality, as was just now noted by Dr. Jones, and I think we also see the potential advantages to the winter seasonality with a fall campaign, because when do we have to worry about the worst overwhelming of the hospitals? It will be when we have influenza, RSV, and potentially COVID at the same time.
And the advantage of this also is that, if we can see influenza vaccine and the COVID 19 vaccines occurring at the same visit, again, it facilitates a vaccination program that may lead to more people getting vaccinated and being protected and reducing the amount of disease we see.
So I think that the overall– this seems like a reasonable way to go.
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3:36:47 PM PETER MARKS, FDA: We’re very much of the mind that we would like to work with our global partners, including WHO and other regulatory agencies, to make sure we’re well coordinated here. It’s just a matter that not every regulatory agency and WHO are not perhaps at the same place right at this very moment.
But ultimately, we totally understand the need to have global surveillance cover– global coverage of these variants, and ultimately good coordination with all of our partners.
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3:37:41 PM JERRY WEIR, FDA: One thing I will add is that the WHO does have a group that monitors variants and at least occasionally makes recommendations. They don’t have a set schedule for when they do this.
About six months ago, they did invite us to join that. And I think that– and we enthusiastically accepted, although it’s still in the works to for it to happen. But we will clearly participate in that if we can work it out.
You’re right, though, that unlike flu, the global distribution of variants is more variable. And that’s one reason I mentioned in my slides, I like that website that’s called co-variants because you can click on every country and you can actually see in real time how this differs.
So going forward, it is still challenging. Variants don’t sweep across the world quite uniform like they do like they seem to with influenza. But yes, we’ll continue to work with our partners throughout the world as best we can.
But our primary responsibility is what’s best for the U.S. market, and that’s where our focus will be.
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3:47:44 PM AMANDA COHN, CDC: I have one question for the companies specifically. I was wondering if you guys could talk a little bit more about immunization in very young children, and if you guys are planning or thinking about doing anything like different schedules and different lengths between doses to align more, in the long term, with our routine immunization schedule? Or if it would be an advantage of having some spacing– some better spacing between the doses to allow for better T Cell responses.
3:48:09 PM RITUPARNA DAS, MODERNA: Yes, maybe I’ll take it first. So we do have a study called BabyCOVE. It is going to be– it started enrolling and we’re dose ranging right now. It’s in infants 3 to 5 months of age. And we are using that eight week interval to try to align with a kind of a routine pediatric vaccinations schedule. And so we’re we’re going to select a dose and then we’ll get into the placebo controlled part of the study.
3:48:47 PM KENA SWANSON, PFIZER: So we are also evaluating in children six months to less than five years of age, both the current dose regimen for the three microgram bivalent vaccine, but also extended intervals. You know, we started in– at the early days of the pandemic with that original schedule. So we’re further studying the longer intervals to see if there’s any impact on the immunity as well.
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3:58:52 PM MARK SAWYER, VRBPAC: Whether the 100 day timeline projected from RNA, from strain selection to product delivery would hold up, if we need single dose vials?
4:00:20 PM RITUPARNA DAS, MODERNA: Sure I can take it first from Moderna. We certainly hear you. And we are moving towards single dose vials and prefilled syringes just to facilitate just that. And we do think we can achieve that in the timeline outlined.
4:00:40 PM KENA SWANSON, PFIZER: Maybe I’ll take it next. So Dr. Swanson here. So similarly, we’ll be transitioning from the multi-dose vial to the single dose vial going forward, and can support that with the future vaccine updates.
4:00:52 PM FILIP DUBOVSKY, NOVAVAX: It’s a similar situation. We’re heading to a unit dose vial, and we’re aiming to get to a pre-filled syringe shortly after that.
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4:03:04 PM JERRY WEIR, FDA: One of the reasons we asked the manufacturers to come to this meeting was to tell us how much time they need. So actually, I heard something today that I hadn’t heard before today, and that was exactly how much time a protein based manufacturer would need.
We may have to go back and rethink this as far as the timing. As I said earlier, I put this out there as a placeholder. We would say– we had an n of one this past year. We did it in June. It seemed to work okay.
But I think, Dr. McInnes, we’re all just going to have to maintain flexibility. You’re right. There’s not– there’s not a good– there’s not a good pattern yet. There’s this– there’s this pattern. And I think we’ll just do that. We will look at this and we’ll try to be flexible. We’ll try to work with manufacturers to keep and get as many manufacturers on the market as we can, because you and I have been through flu for I don’t know how many years.
I mean, having options is important and you never know which one you’re going to need. So we’ll continue to do this. I think, you know, we’ll be flexible and we’ll work with them as best we can.
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4:22:41 PM MELINDA WHARTON, CDC: I am supportive of this question.
I do think there are some data gaps that it will be good to get more information on. I’m glad that there’s more information expected about optimal dosage for children. And there are some questions about different dosages for, say, the primary series and booster for the Moderna vaccine for adults.
There’s some– there’s some unanswered questions and some things to work out. But I think this is absolutely the right thing to do for the program. It will make things simpler. And I know how we ended up this way, but I think this is a good decision to make and I’m supportive of it.
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4:54:01 PM PETER MARKS, FDA: I just wanted to make a correction here. We meant– we don’t mean to limit you to thinking about a two dose series. We wanted to just note that a multiple dose series, as an example, it could be two doses, but that some might have questions about whether it would be more than that, and that in those with compromised immune– I think the main major issue is the concept was if you had documented COVID 19 or if you’ve been vaccinated previously, you would just need one dose versus others who might have multiple doses.
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5:07:07 PM PETER MARKS, FDA: We hear that loud and clear. And in fact, part of the idea of harmonizing things here is to hopefully engage other sponsors to come in and have a variety of different platforms that might be able to be used.
And we also are obviously looking forward to seeing potential platforms come in that might be improvements on the current generation of vaccines.
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5:10:34 PM ERIC RUBIN, VRBPAC: I’m also going to be supportive, as Dr. Chatterjee is, we don’t know what’s going to happen.
I think there is evidence that we’ve seen that there is at least a slight advantage for the Omicron, the better matched Omicron strains that we’re using now, our antigens that we’re using now, and it may be a bigger bang for the buck as these variants become more and more distant, which is certainly what’s going on right now with the XBB strains and the other BA.2s.
I think we want to do it and we’re not going to know how often to do it. I think it’s quite reasonable to think about another one for the fall. I think that’s a very good idea. And there is a limit to how often we can change. But I think that for step one, that would be okay. It’s hard to say that it’s going to be annual at this point.
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5:25:42 PM STANLEY PERLMAN, VRBPAC: So I think there’s a general agreement that updating the vaccine composition is good and that whether it comes to being once a year or how it actually pans out, that we need to have as much information as we can. So we need to have information about how the vaccine is working, epidemiology of the vaccine. We need to keep learning about efficacy, as I just said.
I think we as we said in the first discussion point, we need to have more information still about T cell and B cell and non neutralizing antibody responses so that we can really understand what we’re doing and the combination of different strategies, whether it be protein based or mucosal based.
I was also something to consider, probably not for the fall of 2023, but maybe– maybe for the mixing of the RNA and protein vaccine to something we will need to address then or should address there.
So I think that that’s most of what I would cover. I don’t know if anyone wants to add anything to that. So if not.
DR PRAGNA PATEL, CDC [00:08:47]
So because Evusheld is unlikely to be active against certain subvariants which are now circulating with a high prevalence in the U.S., the CDC is emphasizing steps that immunocompromised persons and their contacts can take to protect themselves. Next slide.
So now that we no longer have Evusheld, we want to reiterate that COVID-19 vaccination remains the most effective way to prevent SARS-CoV-2 infection, associated serious illness, hospitalization and death. In persons who are immunocompromised as well as their household members and close contacts should stay up to date with their COVID 19 vaccination, including the updated bivalent booster, when they are eligible.
Prevention measures such as wearing high quality well-fitting masks, maintaining physical distance from others, improving indoor ventilation, practicing frequent hand washing, and developing a COVID care plan should also be considered. The care plan should include prompt testing at the onset of COVID 19 symptoms and rapid access to antivirals if SARS-CoV-2 infection is detected.
CDC will be releasing an MMWR on Friday summarizing this information in more detail.
12:03:12 PM BRENDAN JACKSON, CDC: You all know well that the Omicron variant XBB.1.5 has attracted a lot of attention in recent weeks as it grew rapidly in the U.S. and until recently, the U.S. has been the only country with a sizable presence of this variant. Lab studies have shown that neutralizing antibody titers have been lower against this variant, than against other recent variants, especially among those who received only the monovalent and not the updated COVID 19 vaccine, raising questions about how well our vaccines will work against it.
In the first MMWR, Dr. Link Gelles and others used the national pharmacy testing program for SARS-CoV-2, known as Increasing Community Access to Testing or ICATT to estimate the effectiveness of COVID 19 vaccines against illness caused by Omicron XBB compared to BA.5 related variants. That is, it’s comparing XBB.1.5 and the other XBBs versus the previous variants that we were seeing before. And this, the time period was from December 1st of last year to January 13th of this year.
It’s important to note that the study did not use whole genome sequencing to classify these variants since the data were not available that quickly, but instead used a sort of a quirk of PCR testing described in the second report.
So bottom line, from this first MMWR is that we did not see reduced vaccine protection against symptomatic illness for XBB and XBB.1.5 compared with those other recent BA.5 variants, quite reassuring. People who received the updated or bivalent COVID vaccines had higher levels of protection than those who received only the previous vaccines with only the monovalents.
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12:05:14 PM BRENDAN JACKSON, CDC: Now, in addition to the MMWRs, CDC is going to be updating our rates of COVID 19 cases and deaths by vaccination status, our web page on the COVID Data Tracker today, which will show that the updated COVID vaccine also reduces the risk of death by COVID 19 by nearly 13 fold compared to those who were unvaccinated.
In those same data, it’s also going to show that people who have the updated booster, the updated vaccine, had over two fold lower rates of death compared with vaccinated people who had not received an updated vaccine.
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12:07:51 PM RUTH LINK-GELLES, CDC: So to answer your first question, I think for vaccine effectiveness, it’s important to think of it as really a population number. It’s hard to interpret it as an individual’s risk because every individual is different, their immune system is different, their past history of prior infection is different. They may have underlying conditions that put them at more or less risk of COVID 19 disease.
And so for all of those reasons, I would think about it more as a population number. And so you could interpret it as, for example, that it cuts your risk of symptomatic infection in about half at the population level.
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12:18:14 PM RUTH LINK-GELLES, CDC: So previous infection is one of those things that’s a little bit hard to measure because people could have completely undiagnosed infection or could have had an at home test that was never reported. So in this study, we did ask people if they had had a previous infection, but what we found is only about a third of them reported a previous infection, which we know is an underestimate from serology data in the U.S., which shows that well over half of adults have had a previous infection.
And so because of that, we didn’t feel it was appropriate to rely on that that information to adjust these estimates. If anything, that under ascertainment of previous infection probably makes the vaccine look on paper worse than it actually is. So if anything, these estimates that we’re publishing are probably underestimates of how well that vaccine is protecting. But it is difficult to measure, for the reasons I mentioned.
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12:20:11 PM RUTH LINK-GELLES, CDC: All of these data inform our understanding of how well the vaccines are working. So the neutralizing antibody data is often the first information that we have, because it can be done relatively quickly and with very few people.
So, often, the neutralizing antibody studies are looking at a dozen or a couple of dozen people for vaccine effectiveness. So looking at that real world protection, that clinical protection against real disease, we need a lot more people. So you’ll see in the paper that some of the some of the analyses had thousands or even tens of thousands of people included in them. And so it just takes longer to get that information, which is why the neutralizing antibody data comes out first and then take it a step further, it takes even longer to get information on more severe disease.
So I think each of these– each of the information, the neutralizing antibody data, the symptomatic infection data and the hospitalization data all help inform our understanding. And the neutralizing antibody data can give us a signal of why we might want to be concerned and dig more deeply. And then in in turn, the symptomatic infection data can also give us a signal to dig more deeply or reassure us.
In this case, I think the symptomatic infection data has so far been relatively reassuring that the vaccines are continuing to work, even with the signal picked up in the neutralizing antibody data. But of course, the vaccines were designed and the vaccination programs goal is really to prevent severe disease and hospitalization. So that’s what we’ll be looking at in the coming months.
We are still waiting to see the proposed changes from CDC and the state. We do plan to align with any changes in the federal definition of qualifying COVID deaths.
Hayley Los Angeles County Department of Public Health
As we realign and organize for improved operations and accountability, we will strive to ensure that our leaders are best able to support these new functions. A new, centralized leadership team of multi-disciplinary experts will reside in the IOD, serve in key lanes of work to support CDC, and provide day-to-day supervision over our organizational units, as well as manage urgent priorities. This new leadership team includes:
These changes will improve efficiency, speed decision-making, and strengthen the communication of scientific information to the American public, ensuring CDC’s science reaches the public in an understandable, accessible, and implementable manner as quickly as possible.
CYRIL GAY, USDA [00:24:19]
So one of the things that that makes this outbreak different today is that we had a phenomenon where we had a virus from wild birds that actually adapted to poultry, like chicken. So even though it’s still within the avian families, those viruses in fact adapt and change genetically when they infect different birds and bird species.
And this is important, because the phenomenon that we face now is something that really never occurred before, where now this chicken-adapted high pathogen avian influenza went back and then spilled back over to wild birds, where now we have wild birds being the source of virus that are now indiscriminately the source of infection across the United States, which is a very different perspective than what we saw in 2014 to 2015. So now we have a different phenomenon. Wild birds, in this particular virus, it’s even more infectious.
And one thing that I would like to leave with you is, yes, we do have vaccines and they’re being discussed. But for agriculture, they haven’t been used because of concern about trade. Because if we start vaccinating our poultry, and we may not be able to differentiate birds that are infected with the virus versus those that are vaccinated. And thereby, when we have to put our documents together that we submit to the World Organization for Animal Health so that we can declare that we are free of the disease, then it’s much more difficult to do. And we have continued restrictions on the trade of our poultry products.
And for those that may not know, the United States is one of the biggest producers of poultry product. We produce over 9 billion chicken meat annually in the United States and export a significant amount of poultry products.
So as they let out all of this information, I’d like you to think about, you know, what would happen if suddenly this virus evolved to be a zoonotic virus. As we know, this has occurred in the past where we had these, excuse me– these H5N1 viruses in Asia that spilled over to people, where these viruses were extremely dangerous and actually caused a high mortality rate.
Now, we’ve been fortunate historically in that this particular virus did not achieve effective human to human transmission. So what about what about if these events occurred? So what’s the message that I’m trying to leave you here is that everyone has a concern, in all of the agencies that are working within the National Biodefense Strategy, that USDA at the moment does their job and does their very best to actually control this current outbreak so that we don’t have further expansion transmission of this particular virus, and so that we can eradicate it, and so that we can mitigate the effects of this particular disease outbreak.
DR ARJUN SRINIVASAN, CDC [02:09:58]
And I’ll just build on what I think that, very briefly, the data gap I think is going to improve dramatically with the new reporting requirement for the antibiotic use and resistance data into NHSN starting in 2024. It will give us required reporting from every hospital, which will include both the isolates that are obtained on admission, as well as isolates that are obtained after the person is in– patient is in the hospital.
So we will have a lot more information and data from about 5,000 hospitals that will be coming in, and I think that will really help. And all of that information, of course, will be accessible to state health departments as well. So we’re not just going to be the ones to see it. They’ll see it at the state and local levels too.
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DR ARJUN SRINIVASAN, CDC [02:41:21]
We have a quite a modeling team now in our division that is focused on a variety of things. They’ve been doing a lot of COVID modeling, but their bread and butter is AMR modeling, right? All the early CRE modeling, all of that work came out of that group. And that group has very, very strong connections to the Center for Forecasting and Analytics. So I think you will continue to see growing use of modeling in AMR work.
CDC does have– we have an expert group called the MInD collaborative. So we now have a funded external group of modeling experts who are focused on infectious diseases modeling, particularly AMR focused modeling. So I think there’s a lot of good work that has come out of that group and that will continue to come that group.
NCHS is not planning to issue new guidance on counting COVID deaths … at least not with regard to those based on death certificates. We are not aware of any changes with regard to case reporting either.
Brian
DR NIRAV SHAH, CDC [00:03:40]
But I’m excited about the challenge and I’m excited to work with Dr. Walensky and her team. My primary job will be to be her alter ego of a sort, to make sure that if she’s tied up, the agency down there is still operating.
But that being said, there are certain areas where Dr. Walensky has asked me to focus: making sure the vast laboratories at the CDC are doing what they need to do to be prepared for the next pandemic, making sure that the data that the agency has are equally robust and ready to inform decision making, to say nothing of the work around communications, policymaking, and just keeping the lights on.
So there’s a lot of work to be done. I’m excited about that next chapter, but I’m equally sad to be departing the Maine CDC.
DR HENRY WALKE, CDC [00:06:24]
On the international front, we did implement over the holidays, pre-departure testing for travelers originating from China, Hong Kong, or Macau. We also increased the number of airports that are covered by our travel based genomic testing program, up to seven airports now. And this is really in response to increased community transmission in China of COVID, and our concern really of potentially emerging of a new COVID variant.
Certainly, pre-departure testing is leaky and won’t prevent all new variants coming into the U.S. that we’re trying to slow transmission there, and also trying to work with other countries to– and including China to increase sequencing in China to better understand if any new variants are emerging. And we’re also through our travel based genomic surveillance program sequencing any new positives.
Right now, all we’re seeing really is Omicron variants or subvariants. So we continue– this is an area that we’re very active in.
NATALIE THORNBURG, CDC [00:15:57]
There’s quite a bit of heterogeneity in the proportion of XBB.1.5 across the U.S. XBB.1.5 really evolved domestically. The first sequence was identified in the United States on October 22nd of 2022. It became predominant in the Northeast during the month of December and is already more than 80% of circulating viruses in regions one and region two. In other regions of the country, it’s much lower in proportion, as low as about 10% of circulating viruses. However, it has been increasing in all regions for the last several weeks. Next slide.
So XBB.1.5 is currently the fastest growing lineage nationally. It’s really the only lineage that’s growing nationally. Its proportional doubling time is somewhere around three weeks, whereas last week’s predicted doubling time was a little bit faster, at about 16 days. It’s still predicted to be growing in every HHS region.
In this model, all other lineages have very slow, near zero, or decreasing growth rates nationally. BQ lineage viruses, which were predominant, are all decreasing in proportion.
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NATALIE THORNBURG, CDC [00:17:30]
There’s been some media attention on a lineage of Omicron called CH.1.1 this week because it’s predicted to have a greater loss in neutralization in compared to XBB viruses. It’s BA.2.75 sublineage and right now it is on the data tracker aggregated with its parental lineage. So it is aggregated with BA.2.75 viruses. It may have a more dramatic loss of neutralization than XBB viruses. And its weighted estimate is currently around 1%. We typically add viruses to the data tracker when the weighted estimate, not the modeled Nowcast estimate, but the weighted estimate reaches about 1%. And we are close to that threshold right now for the week ending December 31st.
However, nationally, it is not increasing in proportion. It is decreasing in proportion. There are a couple of regions where it has some very minor increases in growth, but it is really just above that zero threshold and we don’t expect it to continue to increase proportionally.
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NATALIE THORNBURG, CDC [00:19:10]
Currently there is no data indicating that infection with XBB.1.5 viruses lead to an increase in disease severity. Notably, we have a few upcoming MMWRs in the next few weeks. We have a work group, an interagency work group, called the SARS Interagency Work Group, or SIG, that does risk assessments of newly emerging lineages. We expect to publish in MMWR the framework of that risk assessment, and then present some preliminary data on XBB.1.5. It won’t be a complete risk assessment, because these risk assessments are meant to be iterative. As we get more data, we can update the risk assessment to determine if a new lineage is high risk.
There will also be a manuscript presenting using the S-gene target. There was there was a test that, when Omicron first emerged, that could identify a deletion in the spike gene and we used a S-gene target failure, so a drop out of one of the targets to identify Omicron. The opposite can be done with XBB viruses. It’s not just XBB.1.5, but all XBB, it’s called S-gene target presence. And we can utilize that method to estimate the number of XBB viruses, and that method will be utilized in a third upcoming MMWR to present some very, very preliminary vaccine efficacy data. But it is very preliminary. And it’s not– it’s not quite at least– it’s not quite as precise as more robust methods of vaccine efficacy. So we expect those to be published in MMWR in the next coming weeks.
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NATALIE THORNBURG, CDC [00:21:18]
We expect to have some updated guidance soon, but it’s not been cleared yet and it’s not on our website yet. But I can say, in summary, some of the changes that will be made are a greater emphasis on the utility of using diagnostics for symptomatic patients and asymptomatic persons who have a known exposure to COVID-19, and de-emphasize the need for asymptomatic screening tests, to describe the limitations of some kinds of diagnostic tests, and talk through a little bit more detail on how to interpret test results.
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NATALIE THORNBURG, CDC [00:24:33]
Rapid antigen tests detect viral protein. They use antibodies to detect viral protein. They may be either point of care, that we use it in our homes, or they may be point of care in a clinician’s office, or or they can be used at home. They are less sensitive than nucleic acid amplification tests, but their specificity is very high. Virus has to replicate enough for a lot of protein to be made to be to be detected. And that means that a person can have delayed positivity.
So you’ve probably been hearing a lot of anecdotes, when someone gets symptoms, and they test on a rapid antigen test at home, and then they’re negative and then they go positive with a rapid antigen test a couple a couple of days later. And that’s because they just haven’t made enough viral protein to be detected by these less sensitive tests for those first couple of days.
People can also test positive, not for an extended period of time, the same way as nucleic acid amplification tests, but they can test positive a little bit beyond their infectious period. So people can test positive by these rapid at home antigen test really for up to three weeks, sometimes even four weeks, being a little bit beyond the infectious period, but it’s not quite as dramatic as nucleic acid amplification tests.
Next slide. So these are some of the current pages that are on CDC and they still remain fairly accurate, even though we’re updating to really try to emphasize the importance of using tests for symptomatic and after exposures.
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QUESTION [00:39:55]
Are anything notable about the symptomatology in individuals who have this variant, subvariant, or that we’ve heard about with the CH.1.1?
NATALIE THORNBURG, CDC[00:40:06]
No, it seems like the symptoms are like all other Omicron– there’s really been nothing remarkable about any Omicron lineage virus thus far.
QUESTION [00:40:16]
So in terms of length of infectivity as well, or contagiousness too?
NATALIE THORNBURG, CDC [00:40:21]
Well, I would say it’s probably it’s probably too early to know that. But as far as any descriptive changes in symptoms, severity, nothing seems to be different thus far.
…
QUESTION [00:42:58]
Does that mean it’s going to change the advice for the public around if you’re going to attend a gathering to test asymptomatically? Or would it change anything, or will it be changing anything for health care providers or patients, in terms of coming in before procedures or admit to hospital?
NATALIE THORNBURG, CDC [00:43:17]
Yeah, I really can’t speak to those specifics, but I really think we’re moving towards a direction of saying testing is really important when someone is symptomatic, or when you’ve had a known exposure, and really deemphasizing the need for screening tests in many in many contexts– many, but not all contexts.
QUESTION [00:43:38]
Okay. So we don’t know about the hospital based? You can’t speak today to whether or not new admits or pre-procedure testing for asymptomatic individuals is set to change, is that correct?
NATALIE THORNBURG, CDC [00:43:51]
Not yet. Not yet. But I hope soon that we’ll be able to share that.
…
NATALIE THORNBURG, CDC [00:44:27]
So our best you know, our best proxy for contagiousness is a little bit artificial. It’s really recovery of like culturable virus in a laboratory setting. And it’s not exactly the same thing as person to person transmission, but it’s our best. If we recover culturable virus, that means they are shedding live virus.
So there’s no indication that healthy people with healthy immune systems shed virus, shed culturable virus, beyond day eight, nine, ten. Really the peak shedding of live virus is right around symptom onset, the first couple of days, and then it declines over those first couple of days.
And I can say– and I’ll post in the Q&A, I’ll post a link to some of our older papers, that our ability to recover live virus tends to precede going negative on a rapid antigen test by a couple of days. So it’s not a perfect proxy. It’s okay, the rapid antigen test on the tail end of an infection, but someone really can continue to test positive on rapid antigen test a bit longer than they are shedding culturable virus.
…
DR PRAGNA PATEL, CDC [01:40:35]
So just to quickly summarize, COVID-19 rebound is likely a natural disease process, occurs regardless of vaccination and treatment status, and corresponds with a robust immune response.
Persons on treatment may be at higher risk for rebound, given the drug pressure that suppresses the viral RNA replication, and when it is removed, the virus could reactivate. And this has been seen with other viruses, such as HIV.
Ascertainment bias is also possible, given the fact that persons on treatment are much more closely monitored than persons that are not on treatment.
And it is possible that viral rebound occurs in persons on treatment because they are at high risk of severe disease, and may have host factors that contribute. Risk factors for rebound seem to be somewhat similar to risk factors for severe disease, but little is known currently, and more studies are needed.
TIM UYEKI, CDC [00:18:48]
That doesn’t mean that there’s no influenza viruses circulating in the U.S. There certainly are. Just the level of activity has declined. But we do expect influenza viruses to continue to circulate in the U.S. for weeks to come.
What we have seen this season has been almost all influenza A viruses, very, very little influenza B viruses, and of the influenza A viruses, more than three quarters have been influenza A(H3N2) viruses, with almost a quarter being influenza A(H1N1)pdm09 viruses.
And typically, when we see seasons predominated by influenza A(H3N2) viruses, these tend to be associated with more severe epidemics and particularly have a greater impact on elderly compared to other influenza viruses.
Now, even though we haven’t seen much influenza B activity nationally in the U.S. this season, we often do see a later peak and increase of influenza B viruses, after influenza A viruses have peaked. So it’s actually still unknown whether we’re going to see an increase in influenza B viruses this season.
…
TIM UYEKI, CDC [00:37:49]
This has really tailed off in probably the last five to seven years, but there have been still some sporadic cases, and I’ll just highlight some cases that were reported to WHO last year.
The first case was a worker involved in culling poultry in the U.S. who experienced fatigue. This was someone in Colorado. The only symptom reported was fatigue. No other symptoms. We detected H5N1 virus in one respiratory specimen from this individual, but not from a second collected six days later. He was treated with oseltamivir and fully recovered.
It’s really unclear to me if this represented true infection or more transient deposition of viral RNA. We were unable to isolate the virus from this individual.
But last year there were also two poultry workers in Spain that were working– that were associated with outbreaks of H5N1 in poultry. They were both asymptomatic. They are somewhat more convincing. And there was a prior case in 2020, that was identified in early 2021 from England. Also an asymptomatic person.
So I think asymptomatic infection is plausible, but to the extent it occurs is not clear. It’s probably not that common, but it’s unclear.
And then there was a fatal case in an adult who had poultry exposure in China. That was a fatal case in a relatively young adult. And there was a child in Vietnam who was critically ill, and H5N1 virus was detected. This child had poultry exposure, had consumed poultry that were sick and dead. It’s likely this is H5N1 virus, but that has not been confirmed to date.
And then most recently, really in the last week, there was there was a child who was critically ill in Ecuador in a remote rural area, and H5N1 virus was detected in that child’s respiratory specimens.
…
TIM UYEKI, CDC [00:44:25]
But in terms of the viruses circulating today, they all are descendants of a virus that was first identified in southern China from a goose in 1996. And these viruses have continued to evolve into different what we call clades and sub clades. And since 2020, a particular clade of highly pathogenic avian influenza A(H5N1) viruses are these clades 2.3, .4, .4B viruses, and they have spread via migratory birds in Africa, Asia and Europe.
And late in 2020 into– sorry, late 2021, they spread to North America. And throughout 2022, and we have experienced a lot of poultry outbreaks in the U.S., a lot of wild bird detections, a wide range of of birds, including predatory birds, but also waterfowl.
Of note, late 2022, there was spread to South America. So this is the first time ever H5N1 viruses have really spread into the Americas to cause poultry outbreaks and wild bird deaths. And somewhat concerning is that there’s been transmission to mammals in a variety of terrestrial mammals, which are basically– the most of them are predatory mammals. And it’s thought that they have either been infected and experienced severe illness, and many of them have died, because of finding coming upon dead wild birds. And some some of these have probably consumed dead poultry, but most of it is probably wild birds.
And then there are also unfortunately, marine mammals have also been infected. It’s not quite clear how they have been infected. Some of them could have consumed dead waterfowl.
…
TIM UYEKI, CDC [00:58:16]
Just to say a couple of things to highlight the fact that we’ve had all these outbreaks in poultry of highly pathogenic avian influenza A(H5N1) viruses, but only one individual in the U.S. that I mentioned who had H5N1 virus detected in a respiratory specimen. So CDC is– really the states and local health departments that are leading this, but in terms of reports to CDC, we’re following these, there have been more than 6,000 people who have had exposure to poultry, involved in culling poultry, and some of these people have been had either breaches or not wearing recommended personal protective equipment.
So more than 6,000 people followed, about 160 people to date who have, during this ten day period that have been followed, developed symptoms, and they’ve been tested, and only one individual has been found to have H5N1 virus. The others have had, not surprisingly, other common human respiratory viruses.
So I think the risk– it appears that this virus that’s circulating in birds, it’s causing poultry outbreaks, it’s killing birds, it’s transmitting to some mammals, it appears to transmit really well in birds, but avian to human transmission appears to be very, very uncommon. But it has happened, and I highlighted some cases that have occurred in the last year.
Access to safe, high quality health care is a top priority for the Centers for Medicare & Medicaid Services. CMS requires facilities to meet certain health and safety standards to be certified as a Medicare and Medicaid provider. This includes a requirement to offer residents the COVID-19 vaccines, including any boosters, and educate on their benefits. CMS alerted states to monitor the vaccination rates of their nursing homes by accessing the list of every nursing home with recent resident and staff vaccination rates on the CMS COVID-19 Nursing Home Data webpage.
Enforcement actions, including fines, follow an onsite survey and identification of deficiencies. Sharing the list with states was to ensure they are aware of the vaccination rates in nursing homes to consider for potential investigation of compliance with the requirement to educate all residents and staff on the benefits of the vaccine, and offer to help them get vaccinated. Because this is self-reported data, there may be instances where the zero percent vaccinated in a facility is an error. This is one of the reasons CMS has reminded state regulators to review their data. Any citations for noncompliance with this requirement can be researched by accessing the CMS Quality, Certification & Oversight Reports webpage, selecting nursing homes, then the citation frequency report and selecting F-tag 0887 (in addition to any other criteria you’d like to view).
Have any additional samples have since tested positive? When will it be possible to determine whether they are linked to detections in other countries?
The Public Health Agency of Canada (PHAC) works with public health authorities to investigate positive detections of vaccine-derived poliovirus (polio) in wastewater samples.
PHAC’s National Microbiology Laboratory (NML) has tested wastewater samples collected from August 20 to November 9, 2022. Samples collected during this period all tested negative when they were first analyzed. The sampling sites were selected based on links with New York counties where polio was detected in the wastewater in Summer 2022.
Initial laboratory results from August 2022 that were at first negative for poliovirus were re-tested in December 2022 using an improved test that provided more sensitive results. Using the improved test, NML scientists detected vaccine-derived poliovirus in two samples collected between August 20 and August 30, 2022. Samples collected in September, October and November 2022 were negative for poliovirus. Additional wastewater testing will continue to monitor for signs of poliovirus using the improved test. The sequences are genetically linked to the viruses from the New York State outbreak. PHAC will continue to work with the impacted province and the U.S. Centers for Disease Control and Prevention to investigate the linkages further.
PHAC will continue testing wastewater sites at high-risk locations in consultation with provincial public health authorities.
A high-risk area is one where there are low vaccination rates for polio and/or areas for which there are epidemiological links to cases identified internationally.
Does PHAC believe the samples are from travel-related cases?
A vaccine-derived poliovirus detection in wastewater doesn’t necessarily mean there is local spread of polio. It can mean someone who travelled to an area where vaccine-derived poliovirus was present was infected and returned to Canada. Positive signals are immediately reported to local, provincial/territorial, and international public health authorities and a public health investigation is being conducted to determine:
possible origin; vaccination coverage of the population contributing to the wastewater system; and presence of high-risk groups such as children under 5 or people who are not fully vaccinated.
The overall risk to people in Canada remains very low due to good sanitation and high polio vaccination rates as part of routine childhood vaccination (i.e., 92% for 3 doses or more among 2 year olds in 2019).
PHAC is assisting public health authorities in determining if public health measures may be needed and may expand wastewater testing, if required. PHAC will continue to work closely with public health authorities to monitor the situation, and with global partners like the WHO.
On December 23, 2022, Canada notified the Pan American Health Organization (PAHO) of a detection of vaccine-derived polio virus (VDPV2) in two wastewater samples collected in Canada in August. The polioviruses identified from the sample in Canada are genetically linked to the polioviruses identified from the single paralytic polio case reported in Rockland County, New York, in July 2022. CDC is assisting the investigation to help examine whether these poliovirus sequences have any linkages to other poliovirus detections. CDC will continue to work with Public Health Agency of Canada to investigate the linkages further.
Other than the single paralytic polio case identified in Rockland County, there are no known cases of paralytic polio in the United States or Canada right now. The risk to the public is low because most people are vaccinated against poliovirus during childhood. Access to clean water, good hand hygiene habits and modern sewage systems also help prevent viruses like poliovirus from spreading.
Widespread wastewater testing for poliovirus is not routinely recommended at this time. The best way to protect everyone from polio is to maintain high immunity against poliovirus in the population through vaccination. Adults who aren’t sure they received polio vaccine should speak with their healthcare providers to get up to date.
| Year | First Person | Percent Change |
|---|---|---|
| 2023 | $ 14,580.00 | 7.28% |
| 1994 | $ 7,360.00 | 5.60% |
| 2022 | $ 13,590.00 | 5.51% |
| 1985 | $ 5,250.00 | 5.42% |
| 1991 | $ 6,620.00 | 5.41% |
| 1990 | $ 6,280.00 | 5.02% |
| 1988 | $ 5,770.00 | 4.91% |
| 2007 | $ 10,210.00 | 4.18% |
| 2009 | $ 10,830.00 | 4.13% |
| 2004 | $ 9,310.00 | 3.67% |
| 1989 | $ 5,980.00 | 3.64% |
| 1996 | $ 7,740.00 | 3.61% |
| 2002 | $ 8,860.00 | 3.14% |
| 2019 | $ 12,490.00 | 2.88% |
| 2001 | $ 8,590.00 | 2.87% |
| 1992 | $ 6,810.00 | 2.87% |
| 2013 | $ 11,490.00 | 2.86% |
| 2005 | $ 9,570.00 | 2.79% |
| 1987 | $ 5,500.00 | 2.61% |
| 2012 | $ 11,170.00 | 2.57% |
| 1984 | $ 4,980.00 | 2.47% |
| 2006 | $ 9,800.00 | 2.40% |
| 1999 | $ 8,240.00 | 2.36% |
| 1993 | $ 6,970.00 | 2.35% |
| 2020 | $ 12,760.00 | 2.16% |
| 1986 | $ 5,360.00 | 2.10% |
| 1998 | $ 8,050.00 | 2.03% |
| 1997 | $ 7,890.00 | 1.94% |
| 2008 | $ 10,400.00 | 1.86% |
| 2014 | $ 11,670.00 | 1.57% |
| 2017 | $ 12,060.00 | 1.52% |
| 1995 | $ 7,470.00 | 1.49% |
| 2003 | $ 8,980.00 | 1.35% |
| 2000 | $ 8,350.00 | 1.33% |
| 2021 | $ 12,880.00 | 0.94% |
| 2016 | $ 11,880.00 | 0.93% |
| 2015 | $ 11,770.00 | 0.86% |
| 2018 | $ 12,140.00 | 0.66% |
| 2011 | $ 10,890.00 | 0.55% |
| 2010 | $ 10,830.00 | 0.00% |
| Accession ID | Collection date | Additional location information | Additional host information | Lineage |
|---|---|---|---|---|
| EPI_ISL_16533841 | 1/5/23 | Other: Seattle-Tacoma International Airport, Pooled AN swab | Traveler from China | CH.1.1.2 |
| EPI_ISL_16533844 | 1/5/23 | Other: Seattle-Tacoma International Airport, Pooled AN swab | Traveler from China | BQ.1.1.28 |
QUESTION [00:00:26]
So talk to me about your decision to step down and the timing to do so now– is the fact that you’re leaving now linked to that expected end of the emergency declaration? Does it indicate that the White House is on a kind of new footing when it comes to COVID?
DAVID KESSLER, HHS [00:00:45]
No, I think the commitment is there. I’ve always believed in public service. I grew up in the generation that there was an obligation. It was a privilege to serve. But I also believe you come in and serve and there is a time to leave.
Let me assure you, there is a great team in place that you don’t hear their names at all. You know, the Jason Roos, Kim Armstrong, Steve Cha, Julie Tierney, Lisa Barclay, they are there. They will stay there. And I assure you, this president is fully committed. He’s made sure that we’ve had everything we needed to get us to this point.
It’s been an historic accomplishment what this country collectively has done. You know, my thanks to my predecessors at Operation Warp Speed, never in the history of public health will we ever do what we just did. 660 million vaccines in arms, 13 million antivirals administered, 600 million doses donated. It just is an incredible accomplishment.
Where we are, the virus is not done with us yet. It will still evolve, but I think the chances are low, not nonexistent, but low that it will revert to the kind of mortality that we saw two years ago. To any skeptic, look at those pictures of China. One of the major reasons we don’t look like that is because of the vaccines we have here.
…
QUESTION [00:05:00]
Dr. Kessler, in terms of those treatments, we’ve seen the monoclonal antibodies become less effective, or not effective at all as the virus has mutated. Should we have confidence that, as the virus continues to evolve globally, that we will continue to have antiviral treatments that help us? That reduce the hospitalization rates and keep people from dying once they do get infected?
DAVID KESSLER, HHS [00:05:23]
We have a very effective treatment on the market. It’s not perfect. And no doubt in my mind we have to do everything we can to get another antiviral as soon as we can, just to have it. There’s no guarantees in this business. You and I lived through the antivirals changing the course of HIV. Yes, there’s a great antiviral, Paxlovid, but we need to continue to make sure that that remains the case.
The clinical trials are expected to launch in the coming months. We can certainly alert you, but also know that the announcement will be posted on the RECOVER website. The trials are being designed to treat Long COVID symptoms described by patients as being most burdensome and most important to address. In addition, learnings from studies underway are considered for clinical interventions. The priorities being considered include:
· Viral persistence: When the virus stays in some people’s bodies.
· Autonomic dysfunction: Changes in ability to regulate heart rate, body temperature, breathing, digestion, and sensation.
· Sleep disturbances: Changes to sleep patterns or ability to sleep.
· Cognitive Dysfunction: Trouble thinking clearly or brain fog.
· Exercise intolerance/fatigue: Changes in a person’s activity and/or energy level.
There’s no way to drill down by flight… wastewater is compiled from the international terminal over a 24-hour period. The goal here is to flag the emergence of new variants… the CDC could then employ other testing programs that focus on the origin.
Doug Yakel
…
Hi Alex: yes, we expect to have this in place with the CDC within the next month or two. We’ve already been doing this same process with UCSF for much of the pandemic.
Doug Yakel
GEORGINA PEACOCK, CDC [00:10:32]
The second report shows that national coverage by age 24 months remains strong with most vaccines, and even increased among children born in 2018 and 2019, compared to those born in 2016 and 2017.
This analysis is based on data from the National Immunization Survey-Child, or NIS-Child.
While we continue to monitor the impact of the pandemic, we are encouraged that this report did not identify a national drop in vaccination coverage among children aged 24 months at the beginning of the pandemic.
However, these new findings also reveal persistent and in some cases, widening disparities in coverage. For example, the report found that coverage with the combined seven vaccine series for children living below poverty, or in rural areas, decreased by 4 to 5 percentage points during the pandemic.
The report also found the percentage of uninsured children not vaccinated by their second birthday was eight times that of privately insured children.
…
GEORGINA PEACOCK, CDC [00:12:33]
We believe there are multiple reasons for the declines in vaccination, and we are engaging in numerous strategies to address this.
We need parents, health care providers, schools, and communities to work together with us and state and local health departments to help reduce barriers, increase access, and strengthen vaccine confidence.
To help address pandemic related declines in routine immunization, this week, CDC launched “Let’s Rise” an initiative to equip partners and health care providers with actionable strategies, resources, and data to support getting all Americans back on schedule with their routine immunizations.
…
GEORGINA PEACOCK, CDC [00:22:23]
So I’ll start out at a high level and then I’ll hand it over to Dr. Stokely. So what we have seen over the last two years is a one percentage drop each year in that national coverage for the kindergarten assessment. This is the lowest that we’ve seen in the last decade.
And so that is something to be concerned about. Our Healthy People 2030 goals are to keep that at 95%, and we are below that. So I’ll turn it over to Dr. Stokely to talk a little bit more about those trends.
SHANNON STOKLEY, CDC [00:22:59]
Thanks. And so when we look at the data by state, we do see a wide variation in terms of change in vaccination coverage.
And so looking at MMR, or the measles mumps rubella vaccine, we see that can range from some– the biggest drop in vaccination coverage was 5.4 percentage points. But then we also have states that had an increase in vaccination coverage, and one state, they had over a six percentage point increase in vaccination coverage.
So it’s not that every state had a drop. You know, it did change from state to state.
GEORGINA PEACOCK, CDC [00:23:39]
And the reason it’s important for children entering kindergarten to have the MMR is because we know that, particularly measles, spreads very quickly as seen by two outbreaks that we had last year.
And so the important thing is that all children can be healthy at school and they aren’t being exposed to diseases or vaccine preventable diseases in the school setting.
…
SHANNON STOKLEY, CDC [00:30:33]
What was really interesting and what we found in this report is that we did see an increase in children who are attending school that had no documentation at all, meaning no documentation of vaccination, but also no documentation of an exemption.
And so many of these children are attending school under a policy that’s considered a grace period, also called provisional enrollment. And this is allowing the family to have time to either get their paperwork submitted to the school, or if the child is in in the process of getting their vaccines, giving them enough time to complete all the vaccination series, because there’s some time needed to complete the entire series.
What we’re seeing is that there was an increase in those children who are attending school under those policies. So it’s really not exemptions that are driving this decrease. I think it’s more of a flexibility with the policies that the states may be enacting, because of the pandemic, or for other reasons. But really, I wouldn’t say that exemptions are driving this decrease at this time.
MARIA VAN KERKHOVE, WHO [00:20:23]
So WHO has just published or will be publishing in the next– very, very shortly a risk assessment with advice from the technical advisory group for virus evolution, the TAG-VE, on XBB.1.5. This is one of more than 500 subvariants that WHO is currently tracking worldwide. XBB.1.5 is a further sub lineage of XBB, which you may have also heard about, which is a recombinant of BA.2 sub lineages.
We recently published this risk assessment online, which looks at all available data that we have on this particular variant, looking specifically at growth advantage, looking at immune escape, looking at severity, and making an assessment with available information to determine what we might expect in terms of its behavior and its circulation worldwide.
So the technical advisory group met on the 5th of January, and we’ve had some subsequent meetings with colleagues from U.S. CDC where most of the sequences of XBB.1.5 have been identified, and based on its characteristics, it is part of Omicron, it is an incredibly transmissible variant like all of them are. It does have a growth advantage compared to other sublineages of Omicron, but the data that we have to assess XBB.1.5 is currently very limited and most of the information we have is from only one country, and that’s the United States, and we’re grateful for the information that they have been sharing with us.
So we do know from the available data that it does have a growth advantage. It does have similar properties of immune escape like we’ve seen with XBB. We don’t yet have data on severity, and that is under assessment in the United States, but also elsewhere. The data that we’re looking at is to determine whether or not there’s a change in severity. There’s no indication of an increase or severity or decrease of severity compared to other Omicron subvariants.
…
MIKE RYAN, WHO [00:37:07]
With relation to the United States and XBB.1.5, I think you and the team have been involved in a risk assessment with colleagues on the U.S. side and published it today, the U.S. CDC. So there’s been radical transparency on behalf of the United States in terms of engaging with WHO regarding the the the data and the impact of that data.
PETER MARKS, FDA [00:04:28]
We will probably focus on incremental modifications of these vaccines, at least for the next few years, because I do believe that by the time we have a fundamentally improved vaccine for COVID 19, it’s probably a couple of years away. So right now, we will probably have incremental improvements on the current vaccines, first of all, by making sure we keep up with modifications that address the circulating strains, and then perhaps by seeing the development of vaccines that may try to address more constant regions of the virus and or try to engage more of the T cell arm of the immune system to give more robust immunity.
So those are probably what we will see in the meantime, while we wait for a more robust vaccine. The ability to develop a more effective vaccine that actually is really very good at preventing spread of the virus as well as, of course, then symptomatic disease, would be very much equivalent to where we’re trying to head with the influenza vaccines. And it’s taken– it’s been a decade or more since people have been trying to work on universal influenza vaccines in quite a diligent manner. And yet we still are not right around the corner from having those.
Right now, the national growth projections for XBB.1.5 look similar to what was observed with BA.5 this past summer. However, there are major regional differences in the predicted proportions. In the northeast, XBB.1.5 is predicted to already have reached predominance (>70%), whereas in the midwest and west, it is predicted to be less than 10% of circulating viruses. In this context, there is less room for XBB.1.5 to grow in the northeast than other regions.
Thanks,
LaKia Bryant, MPA
From: LINDMEIER, Christian
Dear Alexander,
Thank you for your interest.
We are expecting the risk assessment coming out from the recent TAG-VE meeting in the next days, but I have nothing more concrete.
| Date | Cumulative courses administered | Difference from previous week |
|---|---|---|
| 01/01/2022 | 7,094,601 | 246,039 |
| 12/25/2022 | 6,848,562 | 236,255 |
| 12/18/2022 | 6,612,307 | 333,191 |
| 12/11/2022 | 6,279,116 | 125,149 |
| 12/04/2022 | 6,153,967 | 183,800 |
| 11/27/2022 | 5,970,167 | 125,887 |
| 11/20/2022 | 5,844,280 | 108,202 |
| 11/13/2022 | 5,736,078 | 106,327 |
| 11/06/2022 | 5,629,751 | 99,145 |
| 10/30/2022 | 5,530,606 | 110,731 |
| 10/23/2022 | 5,419,875 | 62,759 |
| 10/16/2022 | 5,357,116 | ??? |
| 10/09/2022 | ??? | ??? |
| 10/02/2022 | 5,111,611 | ??? |
| 09/25/2022 | ??? | ??? |
| 09/18/2022 | ??? | ??? |
| 09/11/2022 | ??? | ??? |
| 09/04/2022 | 4,489,325 | 173,483 |
| 08/28/2022 | 4,315,842 | 198,776 |
| 08/21/2022 | 4,117,066 | 191,216 |
| 08/14/2022 | 3,925,850 | 246,454 |
| 08/07/2022 | 3,679,396 | 317,848 |
| 07/31/2022 | 3,361,548 | 294,083 |
| 07/24/2022 | 3,067,465 | 287,116 |
| 07/17/2022 | 2,780,349 | 399,703 |
| 07/10/2022 | 2,380,646 | 207,422 |
| 07/03/2022 | 2,173,224 | 308,008 |
| 06/26/2022 | 1,865,216 | 240,085 |
| 06/19/2022 | 1,625,131 | 275,877 |
| 06/12/2022 | 1,349,254 | ??? |
Ocugen intends to work closely with the FDA and other government agencies tasked with pandemic preparedness on the regulatory pathway and the initiation of clinical trials of OCU500, given the immediate need for COVID-19 boosters that can block virus transmission.
We would like to make Ocugen’s mucosal vaccine available as soon as possible and are pursuing opportunities for government funding to support the development of OCU500.
Bharat Biotech licensed the same technology from Washington University and their mucosal vaccine, iNCOVACC®, has been authorized in India, with dosing as a universal booster to begin in the near future. I’ve attached more information on that vaccine for your reference.
It is worth noting that CanSino Bio’s inhaled vaccine, Convidecia Air™, also leverages an adenovirus vectored platform. I’ve attached three papers on heterologous boosting with the Ad5vectored inhalation vaccine. Ocugen is also exploring an inhalation route for its mucosal vaccine.
I have to confess that I am not particularly impressed by anything that is a candidate for the near future. I think that there are a few important considerations. First, an intranasal vaccine has the potential to stimulate mucosal immunity, which is of benefit with regard to reducing transmission. However, my impression is that none of the intranasal vaccines in development are likely to be close to the mRNA vaccines with regard to effectiveness in preventing severe illness, death or even transmission. It has to do with the intensity of the immune response.
Secondly, I would like to reinforce my overall impression that the mRNA vaccine technology is nothing short of amazing. I suspect that the most important factor in the near term will be the ability to generate boosters that will target new variants. The virus is mutating much more quickly and extensively than, for example, influenza virus. As a result, there is very high likelihood that variants that can escape the current vaccines will keep developing. Unfortunately, the major factor in allowing this situation to continue is low vaccination rates and the general reduction in other strategies (such as masking) that are allowing infection rates to stay high.
I’m sorry to not be providing you with a more direct and specific answer to your question, but I don’t see any vaccines on the horizon that are likely to confer immunity across multiple strains of the virus.
Can you clarify if those results have been published anywhere?
We have not yet published the results of the Ph3 trial though plan to in a peer reviewed journal; other data relating to UB-612 has already been published in peer reviewed journals as below: Guirakhoo et al., “High Neutralizing Antibody Levels Against SARS-CoV2 Omicron BA.1 and BA.2 After UB-612 Vaccine Booster,” Journal of Infectious Diseases, 2022 Wang et al., “A novel RBD-protein/peptide vaccine elicits broadly neutralizing antibodies and protects mice and macaques against SARS-CoV-2,” Emerging Microbes & Infections, 2022
Does Vaxxinity plan to pursue licensure of the vaccine in the U.S. with the FDA?
We do not currently have a plan to submit UB-612 for marketing authorization with the FDA. Our current regulatory plan includes submitting for conditional authorization with the MHRA in the UK, and provisional authorization with the TGA in Australia, in the first half of 2023.
[02;25] SEAN TUCKER, VAXART: So we told the world last fall that we were going to work on Omicron specific constructs and evaluate those pre-clinically in Q4 of last year. And our plan was to take some of those things forward, in Q1 of this year.
We have made no announcements yet of the timing of those. But– and I could just tell you that we are still doing some preclinical evaluations, because one of the things we want to find is we want to take forward something that has the best chance of success.
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[04;04] SEAN TUCKER, VAXART: From the pre-clinical standpoint, once we’re done with the pre-clinical evaluation, we’ll start some clinical trials to basically look at what’s called immunogenicity. Essentially look to see if your vaccine produces antibodies and T cells in the blood.
And for us, what we want to know is we’re making antibodies in the nose, because that’s the first line defense, and with a mucosal vaccine, you can do that. And the plan is, once those clinical trials happen, and again, we provided a little bit of guidance back in fall that we plan to start this year.
Then one of the things we’re going to plan on doing is basically test to see if that vaccine is effective. And what we announced is we’re going to partner with the company in the U.K. called hVIVO, I don’t know if you’re familiar with them, but they’re working on essentially what’s called a challenge model.
Essentially, what they do is you would give your vaccine, for us the tablets along with it’s randomized with placebo. Then you wait a certain amount of time and then you give everybody COVID and then count how many people get sick and infected and how long they shed virus. And this way, you could prove that our vaccine is protective, in this case, against Omicron.
That U.K. partner is right now going through a validation stage with that challenge model. And when they’re done, it would be ready for us to use. They have not announced their timing about when they are going to complete that but, assuming everything goes nicely, it happens this year, and potentially we could evaluate our vaccine either this year or next year, depending on the seasonality of things like,whether the facilities are available or whether flu Is getting in the way or something.
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[10;32] SEAN TUCKER, VAXART: We haven’t had the conversations basically with FDA in the U.S. that, hey, if we prove that our vaccine is efficacious, prevents infection, is that going to be enough for us to basically prove the efficacy side of things to basically get approval? So we don’t know that.
It is possible and again, I’m going to point to other countries there. There’s been no efficacy data. And, you know, I’ll point to China and India, and they’ve been able to approve vaccines because the immunogenicity profile looked similar enough to something that’s been approved. So there is precedent outside the U.S..
I don’t think it’s been fully tested in the U.S. with the FDA. Obviously, they take a much more strict approach, so it might be difficult, but I’m not going to say it’s impossible.
[11;24] SPOKESPERSON: But Alex, if you’re asking, do we want to have a vaccine in the United States, the answer is yes.
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[14;04] SEAN TUCKER, VAXART: I haven’t seen anything in the U.S. that’s basically got to the point where it’s phase three intranasal.
I think one of the big challenges then is that the mucosal responses that we have from the stuff that’s been reported, that we’ve been able to find from both China and India, says that those intranasal vaccines aren’t doing a very good job on making antibodies in the nose, which was kind of surprising, but it could be because all these prior kind of virus infections people have had just have made it difficult to get those vaccines to really work as well as they should.
[05;37] J ROBERT COLEMAN, CODAGENIX: So a lot of times, the risk of reversion question– and you can see that with polio, comes from how those traditional vaccines were made, that usually rely on only a few changes to make them– to turn them into a vaccine.
And so people usually are worried about that word that you said, right? Reversion, where you give the person the vaccine, and it actually flips back those mutations to to turn it into the virus that makes you sick.
But the coolest aspect of Codagenix is we make these attenuating mutations, we insert hundreds, so our COVID vaccine has over 250 mutations in it. And so it’s an impossibility for the virus to revert. It cannot revert. It cannot change those changes and jump up in fitness.
And we’ve been able to show that, that genetic stability growth, pre-clinically, in manufacturing, and also in our phase one trial. You could literally pull it out of the nose of all of the participants and show that there was no reversion.
So we think that’s actually one of the strongest suits of our platform and why it’s really a next generation approach for live vaccines is we don’t have that reversion risk.
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[07;52] J ROBERT COLEMAN, CODAGENIX: We do make antibodies. We also make mucosal immunity. We also, and what’s highly differentiating for Codagenix, and what got us into this Solidarity trial in my opinion, is that we could show a very diverse cellular– memory cellular immune response, meaning, we could vaccinate people in our phase one trial, what we did, we actually took out their T Cells, or their PBMCs, we put them in the freezer, this was in 2021.
A year later in 2022, when Omicron emerged, we mixed those T cells with the Omicron virus, and we could show that all of the participants made a response to Omicron. And the reason I emphasized those dates is because it shows, essentially, we make– and what are always the benefits of the live vaccine potential is very broad immunity, right?
We actually show that in our phase one trial, where the participants made an anti-Omicron cellular immune response before the strain even existed. That is a super powerful statement and I think that’s what got us enrolled in the Solidarity trials.
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[09;10] J ROBERT COLEMAN, CODAGENIX: So the Soldarity trial is a phase three trial sponsored by the WHO. It’s being conducted in multiple global locations.
We’re expecting the data to read out sometime in quarter one of this year. And it’s probably one of the last placebo controlled efficacy trials on earth, where we actually show efficacy of the vaccine versus a placebo group with an estimated trial size of about 20 thousand individuals. So it’s a one-to-one with placebo for an intranasal vaccine.
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[10;52] J ROBERT COLEMAN, CODAGENIX: So what’s the coolest thing for me, that gets me super excited?
Codagenix may be the only company to actually show true efficacy against Omicron. Because while the other vaccine players, like Pfizer and Moderna, they can show that their updated vaccine makes antibodies to Omicron, and we know that those antibodies wane, no one’s actually been able to show efficacy against Omicron in the field setting. And so that’s the Codagenix potential, especially with this intranasal delivery.
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[12;07] J ROBERT COLEMAN, CODAGENIX: To add some color there, the reason they probably are not is because they don’t have the ability to run a placebo controlled trial. The U.S. has not come out with the surrogate endpoint, meaning, the amount of antibody you need to show that the vaccine can be licensed.
And so this sort of Codagenix to enter that U.S. market is we are not relying upon a surrogate endpoint. We don’t need the surrogate endpoint for licensure. So we still have the potential to come to the U.S. market because we will actually be able to demonstrate the direct efficacy for our products, and that’s what super highly differentiated, essentially from the entire field, right?
The other 190 second generation vaccines in development, I don’t know if that number is perfectly accurate. What’s so unique about Codagenix is we’re not needing an antibody surrogate endpoint for potential licensure, we’ll be able to show efficacy of our product.
And so the plan will be, most likely the product will be approved ex-U.S. first, simply by the mechanics of our fantastic partnership with Serum Institute India. But that doesn’t preclude us from then bringing the data set, the phase three data set, to the U.S. and pursuing the U.S. market as well.
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[15;24] J ROBERT COLEMAN, CODAGENIX: I mean it’s all sort of demand dependent too. The more demand there is, the more they’ll scale up. I would say they can make millions of doses a day there, if necessary with current infrastructure.
And that was one of the things that we had to show to WHO, that they had the potential to make 300 million doses in less than a year’s time, or have that capacity which they definitely do.
I mean the thing to think about Serum is 65 percent of the world last year got a Serum-manufactured dose. Now that’s not just COVID. That’s also the other vaccines. So their manufacturing process is very large, especially for live attenuated.
[03;06] JOHN BEIGEL, NIH: So I think having a broader protection would be probably a first on the list. And there’s a number of groups working on that.
The other thing is trying to figure out what gives us the longest duration, because there’s cross protection, and then there’s antibody decline, and whether there are any current technologies or emerging technologies that give us longer antibody titers. So those would be lower on the achievability list– they would be next on the achievement ability list.
And then after that comes mucosal vaccine. And I think mucosal vaccines would be what lots of groups are working on. They really think that our current vaccines don’t do a good job at preventing disease and, if we had a mucosal vaccine, it might do better at preventing the transmission. So the mucosal vaccines would be great. That’s just a much harder step to to take.
But there’s a number of groups that are working on those and some of those are, have entered phase one, phase two studies, and there’s been a few that have been licensed, but not not in the U.S. and not based on robust data. So I would still call the field really young, really fragmented, and we need a consolidated effort to really understand how to move mucosal vaccines forward.
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[07;14] JOHN BEIGEL, NIH: So almost everybody now in the U.S. and most of the world is either infected or vaccinated, or both, in many people, multiple vaccines and one or more infections.
So no longer do we have to worry about putting a mucosal vaccine on a naive person. There is a good reason to be skeptical that mucosal vaccines wouldn’t develop as robust systemic immunity in the naive person. But we don’t have to worry about that anymore. With the infections that we have, and the number of people that have been infected, every mucosal vaccine is going to be used on top of an exposed person, whether it’s immunized or infected.
So with that, you would expect some anamnestic response, serologic response, and maybe get better mucosal immune response.
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[09;18] JOHN BEIGEL, NIH: The other thing that I would highlight though is we don’t know how to pick the winners.
So for intramuscular, we know the serologic response, and lots of this work with antibody response, for other coronaviruses, was done many years before COVID ever came out. So we knew when the original efforts to develop a vaccine, we knew how and what to measure. And we knew that we needed to measure the neutralized titer, and then we could say higher neutralizing titers are better, and that’s what we should move forward.
We don’t know what to measure for mucosal. You can measure mucosal IgA, but we don’t know what it means, and we don’t know how to correlate that with disease protection. So part of the challenge of this field is actually trying to figure out not only which ones to move forward, but how do you know if you’ve got a good product? Should we be looking for a serologic response? Should we be looking for a mucosal response? But we don’t know what it means.
But let’s say something has a much better IgA response, is that good enough and should be invested in that, do large trials, just because they’ve got a better IgA response? There’s a lot of work that needs to be done to really help define the optimal candidates.
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[12;24] JOHN BEIGEL, NIH: So if you’ve got a mucosal vaccine, it might generate, you give a vaccine and you compare it to an mRNA vaccine, the mucosal vaccine let’s say, gives, one tenth of the serologic response in the blood but ten times the mucosal response. The FDA won’t know how to interpret that.
So you won’t be able to rest on the laurels of yes, it generated a robust immune response, because It was much less than the mRNAs, but it’s much better mucosally, but it comes back to, we don’t know what that actually means. So it makes the whole field really complicated to interpret and complicated to know which to move forward.
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[16;20] JOHN BEIGEL, NIH: I don’t think there’s a scientific limit. Now interestingly, it becomes increasingly more commercially difficult the more antigens you put in.
So whether there’s, because you basically have to, let’s take mRNA, they would have to make two different mRNAs, and then they mix them for the bivalent. If you had a quadrivalent, you would have to make four different mRNAs and mix them.
So the amount of work to make that vaccine goes increasingly up. So I don’t know where the commercial breakpoint is, if you will, but there probably is more of a commercialization limit than a scientific limit there.
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[18;42] JOHN BEIGEL, NIH: It really is going to be an interesting discussion, because there’ll be a discussion of how to get ahead of the viral evolution. And the FDA took some heat in recommending a BA.4/5 when there was no clinical data on that. And then they pulled the trigger, because they saw the BA.4/5 emerging and they knew that was, or at least they assumed that was going to be the next large wave.
So I think it’s going to be a discussion of how do we push that? If we wait for the virus that we have now, by the time it is put into a manufacturing run, three months from now it is rolled out, that virus is already gone. So how do you get ahead of that? How do you predict viral evolution?
Flu is much better at predicting viral evolution than COVID. That we don’t quite know the rules for COVID. So flu can kind of predict, which of the small, or at least, they’re better at predicting which of these emerging viruses are likely to take off.
So, I think that’s really where the field will go short-term, but that’s kind of, again, using the tools that we have just trying to anticipate the virus a little bit better. So that seems to be the short-term fix as we work on some of these broader activities.
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[20;44] JOHN BEIGEL, NIH: Arguably, I think what you learned is that getting as far ahead as possible probably was the wisest move. So it wasn’t necessarily a lessons learned. It was that there was criticism of the recommendation to move into a BA.4/5 bivalent before there was human data, the WHO was going to the BA.1 bivalent, and when you look at titers with these emerging strains, the BA.4/5 titers seemed to be better than the BA.1 titers.
Sorry, the titers to the new strains from the BA.4/5 seemed to be better than from the BA.1. So getting the furthest antigenically that you can actually was a wise move.
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[22;17] JOHN BEIGEL, NIH: There is, there always is a funding barrier.
But I think what needs to happen is a more consistent, organized program where mucosal vaccines are evaluated. Right now, each company is doing their own, they are testing it in their own lab, there’s not a central lab where all these are tested. They plot it separately.
It’s really hard to compare all this data out there on the mucosal vaccines because it’s just these small little fragments of data done by each company. And I think what needs to happen is a much more organized platform where we start evaluating some of the most promising and figure out how to measure, how to ascertain, which of these are the most likely to be successful.
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[23;54] JOHN BEIGEL, NIH: Right now, we don’t know, even if there was money to move things forward, to really put large amounts of money into a company, or several companies, to move a product forward, I have no idea which ones to bet on.
So it’s really the coordinated effort to get data to understand which of the promising platforms, which are the promising products and the specific companies, but also, which platforms seem to be promising, how do we measure that?
And then if there’s money to support further development, then it’s much easier to say, here, the ones that we think are most useful. Or that’s also where the free market comes and the free markets says, ‘small company, but they’ve got the most useful,’ maybe that it’s easier for them to get investments to move those larger studies for it.
[01;51] STANLEY PERLMAN, UIOWA: That being said, the two problems that people are running into is we really– we can develop vaccine to do these things, but we really don’t have information yet that this is going to actually do what we want, which is to protect us against transmission of new variants or against the future coronaviruses that may come from animals or bats or through intermediate animals to people. So we have a short– we have things we can do, but we don’t know if any of them will really work in the real world. They’re certainly worth trying, but we just don’t know.
And the second thing is that to get these kinds of vaccines up and tested is not trivial because the reason that the vaccines worked so well in 2020 is that the U.S. government supported companies, some of which were large, some of which were not so large, and tested lots of vaccine, so if the vaccine failed, the company didn’t take a huge hit. So that was the second thing.
So both those things need to be in place. We both have to have good vaccines which may work, we don’t know. And we also have to have a way of developing them for large scale use.
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[05;10] STANLEY PERLMAN, UIOWA: Somewhere in between. I’d be enthusiastic if we could show that it worked, but so far we haven’t really done that. And we can do that in mice. We can get responses and some mice are protected, or other experimental animals, and part of the issue may be just the amount of response that one needs.
There’s a lot of studies that in, again experimental animals, that shows that if you increase, if you have a high enough antibody titer, if you have a high enough T cell response, that you actually can prevent disease, but the problem occurs that those kind of levels are not reached in people for the most part. So it’s a great idea, but it’s not– you can’t do that in those single parts of the immune response. You need a total immune response.
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[07;55] STANLEY PERLMAN, UIOWA: Now, if everybody’s been vaccinated, it’s still an issue because it’ll be new people coming out, children coming out, and they will– if we vaccinate only against the viruses that are circulating now, will they be more liable to get infected with ones that were present early in the pandemic, and no longer are present?
So I think that there’s two ways that people think about it. One group says, yep, we should just focus on what we have now, and try to boost our immunity as best we can to what is circulating now and who knows what’s going to come up in the future, but we could do the best we can, or that it will be a mild change.
The other parties might say, let’s continue with bivalent vaccines so we have a broader coverage, even though there’s no evidence now that we really need that broader coverage.
So I think that doesn’t answer your question, because I don’t really know what the very best answer is. I know that I was more of a fan of a bivalent vaccine that was decided in June. But now I don’t know. I think we just have to see how the virus plays out.
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[20;25] STANLEY PERLMAN, UIOWA: I know people working on them. Some of the people I work with actually work on this. Whether it’s going anywhere is another question.
Because they’ve developed methods to inactivate a lot of genes that seem to make the virus more virulent, but there’s so much skepticism about its safety that I just don’t know if that’s going to go anywhere, and by the time you attendeate it so much that we’re not worried about safety, you may not have something that’s very immunogenic. So, you may be– because it’s always a balance between virulence and immunogenicity,
QUESTION: So i guess that’s, maybe to put it bluntly, that’s not on the short term, near term list for you in terms of–
STANLEY PERLMAN, UIOWA: If those others we’re not going to be done next year, this will not be done for a few years.
[01;19] WILLIAM SCHAFFNER, VUMC: If you’re looking for right now, here’s what i have to offer, namely a combination influenza and COVID vaccine. That still looks very optimistic that that might be available for next season, and I think might do something good to combat the vaccine fatigue that’s out there at the moment, and likely to carry over for quite some time.
If we could come to people and say, we can give you one inoculation that will protect you against a whole variety of influenza strains, as well as an updated COVID vaccine, and that’ll make your upcoming Christmas next year much safer, I think that that would be a good message, but that’s what i see in the immediate future.
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[08;16] WILLIAM SCHAFFNER, VUMC: So let’s talk about what the nasal vaccine is intended to do. We know that the virus, when we’re exposed, attaches itself to the cells of the mucous membranes of the quote quote upper respiratory tract, the nose, the back of the throat, and those mucus membranes that line the bronchial tubes that lead down to the lungs. And the whole notion of the nasal vaccine is that there would be a good immunity on that mucosal surface that would actually prevent the attachment of the virus to the cell. Good, that would prevent infection completely, and would also be a barrier to transmission of the virus.
However, we all know that no vaccine is perfect. If the virus were to evade the protection of the nasal vaccine, and get into the cell and start to multiply and infect other cells, well, then we would be in the circumstance we are in today, and we would need protection, because the virus could get into the bloodstream and be sent to other bodily organs and then produce disease and the current vaccines provide those antibodies circulating in the bloodstream, which would then attach themselves to the virus and prevent further dissemination in the body.
I guess the other little piece of information you need is that the current vaccines, which provide antibodies in the bloodstream, those antibodies don’t leak out onto the surface of the mucus membranes very well. So, that’s why they’re not very good at preventing relatively mild illness. But, If that virus then wants to get into the bloodstream and cause more serious disease, that’s when the current vaccines work best. They worked best to prevent severe disease. They’re not– they’re somewhat good, but not very good, in preventing milder disease or transmission from one person to another.
[00;39] PAUL OFFIT, CHOP: The goal of vaccines is to protect against serious illness and that goal continues to be met. Obviously once we hit Omicron and all the Omicron subvariants, which continue to evolve, even though that’s it’s– we haven’t really evolved to anything beyond Omicron, right? I mean, it’s been for a year, it’s been Omicron or Omicron subvariants are all continue to be susceptible to protection against serious disease, whether you’ve vaccinated or naturally infected.
I don’t think the goal is to try and protect against mild disease, because obviously natural infection or vaccination is not going to do that with these immune-evasive strains.
But who cares? You know what I’m saying? Vaccines, you’re just trying to keep people out of the hospital, keep them out of the ICU, keep them out of the wards, so if that’s the goal, we’re meeting it.
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[03;07] PAUL OFFIT, CHOP: So the nasal sprays, you’re protected against mild disease with basically with neutralizing antibodies or arguably binding antibodies through the SC receptor, but antibodies protect you against mild disease. We’re pretty much past that point.
And also frankly, even if this virus never mutated, but frankly all viruses mutate, but let’s say this virus never created variants, and it just was only one strain, then you still wouldn’t be protected against mild disease for long because it’s a short incubation period mucosal infection. The incubation period is only a few days, number one.
Number two is antibodies fade over time, right? So given those two facts, you’re never going to have high titers of neutralizing antibodies for long, so therefore three to six months later, you’re going to be once again susceptible for mild infection. Live with that.
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[04;25] PAUL OFFIT, CHOP: So then the question becomes, would nasal spray vaccines be better? I don’t think so.
For one, yes, you can give a nasal spray vaccine and yes you will get antibodies at the nasal mucosal surface, which will also be short-lived, just like it’s with the intestinal surface for our vaccine. So that too isn’t going to make any difference in any sort of meaningful way about protection against severe disease.
And if you don’t believe that, look at the FluMist experience, i mean FluMist came onto the market in 2003, not exactly a game changer. It’s been on the market for 20 years.
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[09;01] PAUL OFFIT, CHOP: But then I think also, with this bivalent vaccine, which has been as far as I’m concerned, just hopefully something we’ve learned from, where the notion was going to be better protecting against mild disease, better protecting against transmission, that hasn’t been true at all. Nor would you have expected it.
We just keep inadvertently saying, ‘look, we got to do better, this is definitely it,” when in fact we’re doing great.
I mean if you if you’ve gotten three doses of the vaccine, or you’ve gotten two doses of the vaccine and a natural infection, and are less than 75 and otherwise healthy, I think you’re probably good for years. We’ll find out. But that would be the prediction, protection against severe disease.
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[10;07] PAUL OFFIT, CHOP: I’d like to think that we are not going to keep chasing variants. I’d like to think that we’re not going to be recommending a yearly vaccine, which I think also doesn’t make sense. The flu model does not make sense for coronavirus. It doesn’t. It’s not a strain specific phenomenon.
But I don’t know. I mean, I just– because I was at the last meeting, we had back, on June 28th, we discussed bivalent vaccines, and I was one of only two no votes. And I think that was the right vote as it turned out.
But people are kind of carried away with the immediacy of this. I mean the fact is, people are still being hospitalized, people are still dying, and we want to do something. But I think– so I think the thing we should do is we should boost, probably only yearly basis, people who are in those three high risk groups over 75, multiple comorbidities, immune compromise, get them vaccinated.
But also, a lot of people in those groups don’t make a very good immune response. I mean, my 93 year old mother just got another dose of the vaccine. I don’t think that does much for her. I think that what makes more sense for those groups, the people in those groups, is make sure that if you get an infection and you may well, take an antiviral in the first few days, and I don’t think we emphasize that enough frankly.
33;21 MARIA VAN KERKHOVE, WHO: So your second question around the situation in the northeast of the U.S.A. So we don’t have data specifically on severity related to XBB.1.5 and we do note, however, we do note that there is increasing hospitalizations have been reported in the northeast part of the U.S. where approximately 70 percent or so, I should check the exact data, of sequences that are available from that part of the country are XBB.1.5.
What you have to also note is that there are many other respiratory viruses that are in circulation. Not just COVID-19 that is increasing around the world, we’ve just had the holidays, so many people came together, and so we expect transmission to increase. That will result in increasing hospitalizations. We do also have influenza that is in circulation and other pathogens that are in circulation. So we can’t attribute the increase in hospitalizations to XBB.1.5 yet.
But we are working with U.S. CDC colleagues closely and we have asked them for a detailed risk assessment of XBB.1.5 as well, just as we would with any country in any subvariants that are circulating. We need to go deeper and look at the reasons for the increases in hospitalizations and determine what is happening.