Annual? Bivalent? For everyone? Future of COVID shots murky after FDA deliberations

Dr. Peter Marks, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, testifies at a Senate Health, Education, Labor and Pensions Committee hearing on the federal response to the coronavirus on Capitol Hill in March 2021, in Washington, DC.
Enlarge / Dr. Peter Marks, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, testifies at a Senate Health, Education, Labor and Pensions Committee hearing on the federal response to the coronavirus on Capitol Hill in March 2021, in Washington, DC.

The U.S. Food and Drug Administration’s Independent Vaccine Expert Panel met on Thursday to discuss the future of COVID-19 injections. The meeting seemed set for an explosive debate. Earlier in the week, the FDA released documents making it clear that the agency stands firm in its view that COVID vaccines will fit the mold of annual flu shots — with reformulations decided in the first half of each year, followed by fall deployments in anticipation of winter waves.

But outside experts, including some members of the FDA’s advisory board, have questioned almost every aspect of that plan — from the uncertain seasonality of COVID-19 so far, to the futility of looking for rapid variants (or sub-variants, as the case may be). ). Some have even questioned whether it is necessary to stimulate the young and healthy so often when current vaccines offer protection against serious diseases, but only short-lived protection against infections.

A particularly outspoken FDA committee member, Paul Offit, a pediatrician and infectious disease expert at Children’s Hospital of Philadelphia, publicly attacked the bivalent recall, writing a comment in the New England Journal of Medicine earlier this month- Ci titled: Bivalent Covid-19 Vaccines – A cautionary tale. (The FDA advisory committee voted 19 to 2 in favor of bivalent boosters last year, with Offit being one of two votes against.)

Yet, despite the charged context of yesterday’s meeting, the sparks of disagreement were extinguished during a calm discussion. The nine-hour meeting ended with a unanimous vote by the committee in favor of «harmonizing» future COVID-19 vaccine formulations so that primary series and boosters are matched formulations. For example, the primary series vaccines would match the updated bivalent boosters, which currently target both the original strain of SARS-CoV-2 that emerged from Wuhan, China, as well as the omicron BA subvariants. 4/5.


The FDA seemed to soften the waters with questions and talking points focused on «harmonizing» and simplifying COVID vaccines. After the single vote, the agency asked the committee to discuss «simplifying the vaccine schedule,» before moving on to the more perilous, but still sweet, talking point of considering «periodic updates to the composition of the COVID-19 vaccine».

Overall, committee members favored streamlining vaccines where possible, matching primary series injections to booster doses and potentially reducing regimens to one dose for adults and two for high-risk children and adults.

«There’s so much confusion about these different formulations that I think anything we can do to clear up that confusion and make things simpler will be a good thing,» said Archana Chatterjee, dean of Chicago Medical School. and member of the voting committee. said at the end of yesterday’s meeting. «I agree with my other colleagues that there is definitely still a need for these vaccines and we are doing our best to get them in the hands. Having vaccines is not enough, we have to get them. use. … It’s a step in the right direction to get us there.»

But, the most important steps for future vaccines – deciding which formulation should be used next, who should get them and when – remained elephant-sized questions in the boardroom. And even among the relatively placid comments, it was clear that big arguments were bubbling beneath the surface.

Ahead of the vote and committee discussion, advisers listened to a series of presentations from vaccine makers, the FDA and the Centers for Disease Control and Prevention, all of which provided updates on the status of COVID-19. and vaccine performance to date. .

Dive into data

Although Offit and others criticized the bivalent boosters for not being better than previous boosters, data presented at the meeting supported the opposite. Real-world observational data show an advantage for people boosted with the bivalent booster over the original (monovalent) vaccine, even against newer subvariants. Data presented at the meeting show that it outperformed the original vaccine in terms of protection against symptomatic infection, visits to the emergency room or urgent care and hospitalization.

In a CDC study published Wednesday, for example, researchers found that the relative efficacy of the bivalent booster vaccine against symptomatic infection with a BA.5-related omicron subline (which includes BQ.1 and BQ. 1.1) was 52% among people aged 18 to 49. In other words, people in this age group had 52% more protection against infection with BA.5-related strains than people who received the initial booster. For those aged 50 to 64, the relative efficacy against BA.5-related infections was 43% and 37% for those aged 65 and over.

Compared to newer omicron subvariants linked to XBB/XBB.1.5, the relative efficacy against infection was 49% in people 18-49 years old, 40% in people 50-64 years old, and 43% among people aged 65 and over.

Numerous serological studies have also been conducted to compare the antibody responses of the bivalent booster to those of the original booster against the range of omicron subvariants currently in circulation. The results are mixed and, in some cases, difficult to compare due to differences in the interval between vaccinations, the number of people involved and the types of tests used. But overall, the FDA argued that it suggests the bivalent booster provides better neutralizing antibody responses against currently and recently circulating omicron subvariants than the original vaccine.

«The important thing is that the results are all pointing in the same direction,» Jerry Weir, director of the FDA’s viral products division, said at the meeting Thursday. “In other words, with all of these studies, just like those of the manufacturers, there is an enhanced variant-specific neutralization after administration of the bivalent BA.4/5 vaccine compared to the monovalent…I find something unremarkable to see this level of uniformity.»

For example, one of the most recently published studies, published Wednesday in the New England Journal of Medicine, found that a bivalent booster resulted in an approximately three-fold increase in levels of neutralizing antibodies against XBB.1 compared to to people boosted with the original booster. This increase was about the same (3.6 times and 2.7 times) in people without and with prior SARS-CoV-2 infection, respectively.

Despite criticism from Offit and others before the meeting, committee members seemed comfortable with the bivalent data, accepting the FDA’s rosy retrospective.

«I’m totally convinced that the bivalent vaccine is beneficial as a primary series and its boosters,» said David Kim, committee member and infectious disease expert at the Department of Health and Human Services.

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