annual? bivalent? For everyone? The future of COVID shots is murky after FDA deliberations

The FDA’s panel of independent vaccine experts met Thursday to discuss the future of COVID-19 shots. The meeting seemed set for a heated discussion. Earlier in the week, the Food and Drug Administration issued a docs He made it clear that the agency sticks to its idea that COVID vaccines will fit the mold of annual flu vaccines— with recasting decisions in the first half of each year, followed by fall rotations in anticipation of winter waves.

But outside experts, including some members of the FDA’s advisory committee, have questioned nearly every aspect of that plan — from the so far uncertain seasonality of COVID-19, to the futility of chasing fast-moving variants (or sub-variants, as the case may be). .). Some have even questioned whether young people and their health need to be boosted more frequently when current vaccines offer protection against severe disease, but only short-term protection against infection.

One outspoken member of the FDA panel, Paul Offit, MD, a pediatrician and infectious disease expert at the Children’s Hospital of Philadelphia, has publicly attacked the bivalent booster, writing a commentary in the New England Journal of Medicine earlier this month titled: Bivalent Covid-19 Vaccines – A Cautionary Story. (Food and Drug Administration Advisory Committee Voted 19-2 in support of bivalent reinforcements last year, with Offit being one of two dissenting votes.)

However, despite the charged background of yesterday’s meeting, sparks of disagreement fizzled out over a quiet discussion. The meeting is nine hours It culminated in a unanimous vote by the committee in favor of “harmonizing” future formulations of COVID-19 vaccines so that primary series and boosters are compatible. For example, the initial vaccine series will match updated bivalent boosters, which currently target both the original strain of SARS-CoV-2 that emerged from Wuhan, China, as well as the omicron subclass BA.4/5 variants.

simplification

The Food and Drug Administration appears to have toned down questions and discussion topics that focus on “harmonizing” and simplifying COVID vaccines. After the one-on-one vote, the agency directed the panel to discuss “streamlining the immunization schedule,” before moving on to the more serious, but still gentle discussion topic, consideration of “periodic updates to the composition of the COVID-19 vaccine.”

In general, the committee members favored simplifying vaccines where possible — having the initial series doses match booster doses, and perhaps trimming the regimens down to one dose for adults and two for children and high-risk adults.

“There is so much confusion around these different formulations that I think anything we can do to mitigate that confusion and make things simple, would be a good thing,” said Archana Chatterjee, dean of the Chicago Medical College and a member of the voting committee. He 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 everything we can to get them into arms. Getting vaccines is not enough, we need to use them.… This is a step in the right direction to get us there.”

But the bigger steps for future vaccines — deciding what formulation to use next, who should get it, and when — have remained elephant-sized questions in the boardroom. And even among the relatively quiet comments, it was clear that major disagreements were beneath the surface.

Before the committee vote and debate, the advisors heard a series of presentations from the vaccine makers, the Food and Drug Administration, and the Centers for Disease Control and Prevention, all of which provided updates on the status of COVID-19 and the vaccines’ performance to date.

Dive into the data

Although Offit and others criticized bivalent reinforcers for not being any better than previous reinforcers, data presented at the meeting argued otherwise. Real-world observational data shows an advantage for people boosted with the bivalent booster over the original (monovalent) vaccine – even against more recent sub-variants. Data presented during the meeting shows that it has outperformed the original vaccine in terms of protection against symptomatic infection, emergency department or urgent care visits, and hospitalization.

in The CDC study was published WednesdayFor example, the researchers found that the relative efficacy of the bivalent booster vaccine against accidental infection with the Omicron sub-strain associated with BA.5 (which includes BQ.1 and BQ.1.1) was 52 percent among people ages 18 to 49. In other words, people in this age group had 52 percent more protection against infection with BA.5-related strains than people who received the original booster. For ages 50 to 64, the relative efficacy against infection associated with BA.5 was 43 percent, and it was 37 percent among those 65 and older.

Against the newer XBB/XBB.1.5-associated sub-variants, the relative efficacy against infection was 49 percent among 18- to 49-year-olds, 40 percent among 50- to 64-year-olds, and 43 percent Among those 65 years of age or older.

There have also been a large number of serological studies examining how antibody responses to a bivalent booster compare with those to the original booster when encountering the currently circulating Omicron sub-series variants. Results are mixed and, in some cases, difficult to compare due to differences in the intervals between vaccinations, the number of subjects involved, and the types of assays used. But overall, the FDA has argued that it indicates that the bivalent booster provides better antibody responses against sub-Omicron variants currently and more recently in circulation than the original vaccine.

“The important thing is that all of the results are heading in the same direction,” Jerry Ware, director of the FDA’s Division of Viral Products, said at the meeting Thursday. In other words, with all of these studies just like those done by the manufacturers, there is improved neutralization of a specific variant after administration of the BA.4/5 bivalent vaccine compared with the monovalent vaccine… I find it rather remarkable to see this level of standardization. “.

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

Despite criticism by Offit and others before the meeting, committee members seemed comfortable with the bivalent data, and accepted a rosy retrospective for the FDA.

“I am absolutely convinced that the bivalent vaccine is useful as a primary series and boosters thereof,” said panel member David Kim, an infectious disease expert with the Department of Health and Human Services.