FDA to allow new Covid boosters without human trials

Updated Covid vaccine reminders, a reformulated version targeting the BA.5 omicron subvariant, might be available around Labor Day. These will be the first Covid vaccines distributed without human trial results. Is it important?

Because the Biden administration pushed for a fall recall campaign to begin in September, mRNA vaccine makers Pfizer-BioNTech and Modern only had time to test the reformulated injections on mice, not humans. That means the Food and Drug Administration is relying on data from mouse trials — as well as results from human trials of a similar vaccine that targets the original omicron strain, called BA.1 — to evaluate new vaccines, according to a recent tweet from FDA Commissioner Dr. Robert Califf.

It could be a potentially risky bet, experts say, if the shots don’t work as well as expected.

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The FDA’s bet on new Covid boosters

Federal health officials hope the new vaccines will offer stronger protection compared to existing booster shots, which still target the original coronavirus strain. But the lack of data in humans means officials are unlikely to know how much better the new vaccines are — if at all — until the fall booster campaign is well underway.

FDA’s decision to move forward without human trial data is a gamble, experts say, threatening to sue declining public confidence in vaccines if the new boosters don’t work as expected.

“There’s no reason to think they won’t be safe,” said Dr. Celine Gounder, an infectious disease specialist at NYU Langone Health in New York. “But will they provide significantly greater protection than the original vaccines? Of this I am skeptical.

When the FDA cleared the early versions of Covid vaccines from Pfizer and Moderna in late December 2020, it based its decisions on safety and efficacy data from tens of thousands of volunteers.

The new vaccines from Pfizer and Moderna are so-called bivalent vaccines, designed to target the BA.4 and BA.5 omicron subvariantsas well as the original strain of the coronavirus, in a single dose.

Due to high levels of immunity to previous vaccination and infection, it would be impossible for companies to test the new boosters on nearly as many people as the original vaccines.

The FDA asked drugmakers to update the vaccines in late June, with the goal of having the vaccines tested and distributed by the fall. Moderna has completed registration for its new booster with 512 participants. Pfizer said it began human testing at the end of the month.

Both companies are expected to report results later this year.

The FDA’s decision to consider Covid recalls without human data is consistent with how it evaluates modified flu vaccines each year. Clinical studies in humans are not required for approval of seasonal flu vaccines, even when reformulated for strain changes, said Dr. Jesse Goodman of Georgetown University, former chief of FDA vaccines.

Still, the flu vaccine is not a fair comparison, said Dr. Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia.

The FDA’s flu vaccine policy is based on decades of experiments with strain switching where flu vaccines have generally behaved the same. The United States is still in its first iteration of Covid vaccines, and mRNA technology has only been widely used since late 2020.

The agency makes “huge assumptions” in its review of new Covid reminders, Offit said, adding that new vaccines may not be more effective than existing vaccines.

Not all experts see it the same way.

Dr. Peter Hotez, co-director of the Center for Vaccine Development at Texas Children’s Hospital, said updating boosters to match circulating strains made sense.

“In an ideal world, there is an advantage to combining BA.5 with the original line because BA.5 is still with us,” Hotez said. “And if there is a concerning new variant that emerges later this fall or winter, it may look more like BA.5 than the original line.”

New Covid boosters are likely to work better than existing ones, but uncertainty will persist until human trials are complete, Hotez said.

Animal data is useful, he said, but there are pitfalls in relying solely on this type of data.

If you are over 50 or over 12 and immunocompromised and more than three months away from a previous Covid vaccination or infection, you should receive a Covid vaccine booster this fall.

Dr. Céline Gounder, NYU Langone Health

“The pitfalls are that animals are animals and humans are humans, and while there are overlaps, sometimes there are surprises,” Hotez said. (Children’s Hospital and Baylor College of Medicine have developed a low-cost vaccine, called Corbevax, which has been licensed for use in India.)

Gounder, of NYU Langone Health, agreed, pointing to a study published this year in the journal Cell Reports who found that vaccine-induced antibody responses in mice may differ from antibody responses seen in non-human primates and humans. This study looked at neutralizing antibody responses to beta and gamma variants, two earlier versions of the virus that spread in the United States but never became dominant.

The authors suggested that caution should be exercised when interpreting data obtained from animals.

But what about the human data of the BA.1 boosters?

Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston, added that using data from the BA.1 booster can also only provide limited value in determining the effectiveness of reminders BA.5.

Barouch, who helped develop Johnson & Johnson’s Covid vaccinenoted that this version of the boosters in the published data showed only marginal improvement in immune responses against the original omicron variant compared to the existing boosters.

The clinical benefit of the BA.5 booster over existing vaccines “is unclear”, he said.

Who needs a booster?

Despite the uncertainty surrounding the new recalls, most experts agreed that Americans should get the vaccine offered to them this fall and winter.

Many Americans “need a refresher,” Hotez said.

It will be especially important, they said, that those most at risk get vaccinated.

“Overview: If you are over 50 or over 12 and immunocompromised and more than three months away from a previous vaccination or Covid infection, you should receive a booster Covid vaccine this fall,” Gounder said. .

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