HUNT VALLEY, Md. (TND) — New COVID-19 booster shots could be administered to Americans within days, and they target both the original strain of COVID and the newer omicron subvariants, which are now dominating cases in the U.S.
The Food and Drug Administration authorized the tweaked boosters Wednesday. Once the Centers for Disease Control give the green light, Pfizer will roll out its booster for those 12 years and older, and Moderna for those 18 years and older. Those individuals will have had to have gotten the two original, primary doses of vaccine, but they need not have gotten one or two of the previous booster shots. The government’s already ordered 175 million doses of the bivalent booster.
But the new boosters come with a caveat — drugmakers and federal agencies don’t have data from clinical trials yet, meaning the booster shot is being authorized without data showing it’s safe and works in humans. The only data available is from mice testing.
It’s the first time the FDA has based its decision off such data over human data, and it’s stirring debate among experts, both over the safety and over federal agencies’ credibility among Americans.
Why the shortcut?
Health officials want to improve COVID boosters ahead of the fall and winter to prevent severe disease and deaths, and data shows omicron subvariants are able to evade immunity. The United Kingdom seemingly beat the U.S. to bivalent vaccines, approving a new booster earlier this month that targets the original strain of the virus and the original omicron variant, BA.1.
But, that wasn’t good enough for the FDA, which rejected a BA.1 bivalent booster last spring. Although the BA.1 bivalent vaccines were already being produced by companies like Moderna and Pfizer and BioNTech, the FDA told them to reroute and target the rapidly emerging BA.4 and BA.5 subvariants. The updated booster combines mRNA from the original SARS-CoV-2 spike protein with mRNA from the spike protein of the two subvariants.
“Given the ongoing evolution of SARS-CoV-2 and its variants, it’s of great importance that vaccines can be rapidly adapted to the major circulating omicron lineages,” said BioNTech CEO and Co-Founder Dr. Ugur Sahin.
Pushback
Roughly a month ago, an FDA advisory committee voted 19-2 to approve use of COVID boosters based on an omicron variant sequence. The two “no” votes were cast by Paul Offit from Children’s Hospital of Philadelphia and Hank Bernstein of the Zucker School of Medicine. Offit, along with American virologist and professor at Cornell University, John Moore, penned an op-ed titled, “FDA: Don’t rush a move to change the COVID-19 vaccine composition.”
Their argument is both omicron boosters and early variant boosters are “little or no better than a standard booster.” BA.1 versions were tested as boosters in animals and also in small-scale human trials. The scientists point out two to four weeks after the BA.1 booster shots, neutralizing antibody levels against omicron BA.1 were roughly twofold higher than with the original vaccine. Moderna’s two-component omicron variant plus original booster vaccine showed higher antibody levels, but by less than twofold. Pfizer’s two-component vaccine performed less well than an omicron-only booster.
“Even allowing for the nature of very early data, the story on two-component vaccines is far from clear,” Offit and Moore wrote. “What is known is that the increasingly prevalent BA.4 and BA.5 variants are even more resistant to neutralizing antibodies, typically by three- or four-fold, than the now-vanished BA.1 variant on which the omicron vaccines are based. The trend toward greater resistance of neutralizing antibodies may well worsen.”
They argued a booster based on the new subvariants will only modestly increase the levels of neutralizing antibodies from the levels in the standard vaccine, and it’s not enough to justify a switch. They compare this difference to the slight difference between the original Moderna and Pfizer vaccines — they provide nearly identical protection against mild to severe COVID-19, but the benefits of Pfizer wane a little bit faster over time. Offit and Moore wrote federal agencies still don’t have full datasets from all variant booster trials to make an informed decision about whether, and to what extent, the “slightly superior neutralizing antibody response to omicron-based boosters translates into significantly greater protection against BA.4/BA.5-mediated infections and severe or fatal disease.”
“If an omicron-based booster provides little advantage over the vaccine stocks that already exist, is it worth the switch?” the scientists said. “Making and rolling out an entirely new supply of COVID-19 vaccines on a nationwide basis is no trivial matter, particularly when Congress seems reluctant to provide the funds.”
Another choice raising eyebrows is the FDA didn’t convene a meeting of advisers before authorizing this new round of booster shots. The advisers met in June, which is when they voted in support of targeting the new variants, but officials didn’t meet with advisers again before authorizing the shots and distributing them to millions of Americans.
Offit separately told the Wall Street Journal, “I’m uncomfortable that we would move forward — that we would give millions or tens of millions of doses to people — based on mouse dataIf you have some evidence that this is likely to be of value, sure. But if you don’t have evidence, and you know that the current vaccine does offer protection against severe disease, I don’t think it’s fair to ask people to take risks.”
Moore added to USA Today, “To rely only on mouse data (for authorization) would be unprecedented in my knowledge and would certainly raise eyebrows. It doesn’t mimic the human situation.” He said he’s concerned about the public, who may be expecting the new booster to prevent more infections. “They’re offering the public a shiny toy and they say, ‘Look, here’s a new shiny toy, go out and get boosted with it. What if the public realizes the shiny toy doesn’t come with the battery included? Will that reduce confidence in future vaccines?”
Defending the move
FDA Commissioner Dr. Robert Califf posted a thread on Twitter detailing the logic being used by the agency to rapidly authorize these new boosters. He wrote the FDA is relying on the “totality of available evidence” in its decision, including: clinical trial data from other bivalent mRNA COVID-19 boosters; real-world evidence from current COVID-19 vaccines administered to millions of people; and non-clinical data for the bivalent BA.4/5 vaccines.
“Bivalent and multivalent vaccines are very common and modifying a vaccine to include different virus strains often does not require a change in other ingredients,” Califf tweeted. “FDA has extensive experience with reviewing strain changes in vaccines, as is done with the annual flu vaccine. Real world evidence from the current mRNA COVID-19 vaccines, which have been administered to millions of individuals, show us that the vaccines are safe. As we know from prior experience, strain changes can be made without affecting safety.”
He added about the FDA’s decision to scrap the advisers’ meeting that “the agency feels confident in the extensive discussion that was held in June,” where the advisers “voted overwhelmingly” to include an omicron component in the boosters, and “FDA has no new questions that warrant committee input.”
Offit argued against Califf’s comparison of the new boosters to the flu vaccines. He told the Journal flu viruses mutate so quickly that shots from one year don’t offer protection to the next, but the currently available COVID-19 shots still keep people out of the hospital.
Why now?
A significant reason behind the FDA’s decision is a race against the clock — and the Biden administration’s planned booster campaign this fall.
“If we waited for clinical trial results, thank you very much, we’d get them in the spring. This is just an updating of the previous vaccine that we used,” William Schaffner told the Journal. Schaffner is a professor of medicine at Vanderbilt University Medical Center and a nonvoting liaison to the CDC committee — which will decide whether to recommend the shots now that the FDA gave them a thumbs-up.
Many health officials say the country has enough experience with vaccines at this stage to be confident in the new boosters, and time is of the essence. Dr. Ofer Levy also advises the FDA and is a pediatrics and infectious disease researcher at Harvard Medical School. He told NPR, “We have 500 people a day dying of coronavirus right now. Those numbers sadly might very well rise in the fall and the winter. The question is: ‘Can we do something better?’ And I think the answer is: ‘We can, by implementing this approach.’”
Proponents of the updated vaccines consistently point to the fact the new booster will be identical to the original vaccine, only adding genetic coding for two versions of the protein the virus uses to infect cells, from the BA.4/5 subvariants.
“We’re going to use all of these data that we’ve learned through not only from this vaccine but decades of viral immunology to say: ‘The way to be nimble is that we’re going to do those animal studies,’” said Deepta Bhattacharya, an immunobiologist at the University of Arizona College of Medicine. “We’re really not going out too far on a limb here.”
Dr. Anthony Fauci, who’s heading out of his role as Biden’s chief medical adviser and director of the National Institute of Allergy and Infectious Diseases at the end of the year, called the BA.5-specific booster shots the country’s “best guess” for dealing with COVID-19 this call.
“There’s always the possibility that you’re going to have the evolution of another variant,” Fauci said. “And hopefully, if that occurs, it will vary off from the BA.5 only slightly — in the sense of being a sub-sub-lineage of it, and not something entirely different. That’s the situation you always face when you’re dealing with a moving target.”
The CDC is the final hurdle before shots can start going in arms. An advisory panel is set to debate the evidence Thursday, and discuss if high-risk populations should get the shots first. Pfizer said it could ship up to 15 million of its doses by the end of next week.
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