Yearly? Divalent? for all? Future of COVID shots uncertain after FDA talks

Yearly?  Divalent?  for all?  Future of COVID shots uncertain after FDA talks
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Dr.  Peter Marks, director of the Center for Biological Evaluation and Research within the Food and Drug Administration, testifies during a Senate Health, Education, Work and Pensions Committee hearing on the federal coronavirus response on Capitol Hill in Washington, DC, in March 2021.
expand / Dr. Peter Marks, director of the Center for Biological Evaluation and Research within the Food and Drug Administration, testifies during a Senate Health, Education, Work and Pensions Committee hearing on the federal coronavirus response on Capitol Hill in Washington, DC, in March 2021.

The US Food and Drug Administration’s committee of independent vaccine experts met on Thursday to discuss the future of COVID-19 vaccines. The meeting seemed poised for explosive discussion. Earlier in the week, the FDA released documents this made it clear that the agency remained true to its idea. COVID vaccines to fit annual flu shot pattern– with reformulations agreed in the first half of each year, followed by fall commissioning in anticipation of the winter waves.

But outside experts, including some on the FDA’s advisory committee, have questioned nearly every aspect of this plan, from the so far vague seasonality of COVID-19 to the futility of chasing fast-moving variables (or subvariables, as the case may be). ). Some have even questioned whether there is a need to boost the young and healthy so often at a time when current vaccines protect against serious disease but only short-term protection against infection.

A particularly outspoken member of the FDA committee, Paul Offit, a pediatrician and infectious disease specialist at Children’s Hospital of Philadelphia, publicly attacked the bivalent enhancer, writing a commentary in the New England Journal of Medicine earlier this month: Bivalent Covid-19 Vaccines – A Cautionary Story. (FDA’s advisory committee voted 19-2 to support two valuable supporters last year, Offit was one of the two votes against.)

Still, despite the tense history of yesterday’s meeting, sparks of disagreement were extinguished over a calm discussion. nine hour meeting resulted in a unanimous vote by the committee in favor of “harmonizing” future formulations of COVID-19 vaccines so that primary series and boosters are matching formulations. For example, primary series vaccines will mate with updated divalent enhancers targeting both the original SARS-CoV-2 strain currently originating from Wuhan, China, and the omicron subvariants BA.4/5.


The FDA seemed to have softened the ground with questions and discussion threads focused on “harmonizing” and simplifying COVID vaccines. After a single vote, the agency led the committee to discuss “simplifying the vaccine program” before moving on to the more dangerous but still gentle discussion of “periodic updates to the COVID-19 vaccine composition.”

Overall, committee members opted to modernize vaccines where possible—making primary series shots match booster doses, potentially reducing regimens to one dose for adults and two for children and high-risk adults.

“There is so much confusion about these different formulations that I think anything we can do to clear up this confusion and simplify things would be a good thing,” said Archana Chatterjee, Dean of the Chicago Medical School and a voting committee member. she said at the end of yesterday’s meeting. “I agree with my other colleagues that these vaccines are absolutely needed and we will do our best to arm them. It’s not enough to get vaccinated, we have to get it. … It’s a step.” in the right direction to get us there.”

But the bigger steps for future vaccines—deciding which formulation to use next, who should get it, and when—remained elephant-sized questions in the boardroom. Even amongst the relatively calm comments, it was clear that major discussions were bubbling beneath the surface.

Prior to the committee’s vote and debate, consultants listened to a series of presentations from vaccine manufacturers, the FDA and the Centers for Disease Control and Prevention, all of which provided updates on the state of COVID-19 and the performance of vaccines so far. .

data dive

While Offit and others criticized the bivalent boosters for not being any better than previous boosters, the data presented at the meeting argued otherwise. Real-world observational data suggest an advantage for people augmented with the bivalent enhancer compared to the original (monovalent) vaccine, even against the newer subvariables. Data presented during the meeting show that it surpasses the original vaccine in terms of protection against symptomatic infection, emergency room visits or urgent care visits, and hospitalization.

Inside and the CDC study published WednesdayFor example, the researchers found that the relative vaccine efficacy against symptomatic infection with the BA.5-related omicron sublineage of the bivalent enhancer (includes BQ.1 and BQ.1.1) was 52 percent in subjects aged 18 to 49 years. In other words, people in this age group had 52 percent greater protection against infection with BA.5-related strains than people who received the original booster. The relative efficacy against BA.5-related infection was 43 percent among those aged 50 to 64 years and 37 percent among those aged 65 and over.

Against the newer XBB/XBB.1.5-related omicron subvariants, the relative efficacy against infection was 49 percent in people 18 to 49 years old, 40 percent in people 50 to 64 years old, and 43 percent in people 65 years and older.

In addition, numerous serology studies have looked at how the antibody responses of the bivalent enhancer against the gamut of currently circulating omicron subvariables compare to those of the original enhancer. Results are mixed and in some cases difficult to compare due to differences in intervals between vaccinations, the number of individuals involved, and the types of assays used. But overall, the FDA argued that they suggest that the bivalent enhancer 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 going in the same direction,” said Jerry Weir, director of the FDA’s Viral Products Division, at the meeting Thursday. “In other words, in all these studies, just like the manufacturers’, there is enhanced variant-specific neutralization following administration of the bivalent BA.4/5 vaccine compared to the monovalent vaccine… I find it somewhat remarkable to see this level of uniformity.”

For example, one of the most recently published studies Wednesday in the New England Journal of Medicinefound that a bivalent supplement resulted in a roughly three-fold increase in neutralizing antibody levels to XBB. This increase was roughly the same between subjects with and without prior SARS-CoV-2 infection (3.6-fold and 2.7-fold, respectively).

Despite criticism from Offit and others prior to the meeting, committee members seemed comfortable with the two-value data, accepting the FDA’s pink retrospective.

“I am fully convinced that the bivalent vaccine is useful as a primary series and its promoters,” said committee member David Kim, an infectious disease specialist in the Department of Health and Human Services. Said.

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