Troubled by waning immune protection against the COVID virus, this fall’s vaccine booster should be a redesigned two-strain version, according to a recommendation by the FDA’s panel of experts on Tuesday.
The new recipe – which would contain the genetic code for both the original strain and an omicron strain – would be a better match against the evolving pathogen, they said.
“We’re trying to get ahead of a virus that has been very crafty,” said Dr. Peter Marks, who oversees vaccine regulation at the FDA. “The benefits outweigh the risks of making this change.”
The vote comes as California’s COVID-19 positivity rate continues to climb, surpassing anything the state has seen this year. The California Department of Public Health on Tuesday reported the statewide positivity rate at 13.2%, up from 11.4% the previous week, as new, more transmissible variants grow throughout the state.
Public health experts are braced for a larger surge in cases this fall and winter, as people head indoors.
Existing vaccines, based on the original one-strain version of the virus, still prevent death. But there are a growing number of so-called “breakthrough” cases – and, more worrisome, some older people are getting seriously ill, despite vaccination.
Public health experts blame the fast-spreading omicron subvariants BA.4 and BA.5, which now dominate the U.S., representing 52% of all new infections, according to CDC data. Because they can partially evade immunity, they are 10% more transmissible than the earlier BA.2 subtype.
If these trends continue, more hospitalizations are expected, according to statistical models presented by Justin Lessler, a professor of epidemiology at the University of North Carolina at Chapel Hill. “And particularly with a variant,” he said, “we do see a substantial probability of resurgences in the fall.”
Between 95,000 and 211,000 people could die of COVID between March 2022 and March 2023, Lessler said.
The advisory panel did not address who would be first in line for the new vaccine, but it is likely that people over age 50 who have already received two doses would be offered the initial doses, said Marks.
The FDA has the final word on vaccine strategy, but it typically follows the panel’s recommendations.
The decision creates a logistical challenge: Manufacturers must quickly produce enough of the new vaccine to help fend off next winter’s anticipated surge. If the panel had stuck with existing vaccines, there are abundant supplies. A delayed rollout means lost lives.
Doses of modified vaccine could cost the federal government about $5 billion to $12 billion, one senior federal official told The New York Times.
At the meeting, Pfizer said it could have the new product available in the first week of October. Moderna said its vaccine would be ready in late October or early November. Novavax, which hasn’t yet received an emergency use authorization for its vaccine, said its existing product is able to protect against new variants but that an updated vaccine would be available “in the fourth quarter of the year.”
The committee of largely outside experts voted 16 to 2 for the booster after daylong public debate about complex data that compared the effectiveness of different vaccine formulations against different variants.
The two “no” votes were cast by Dr. Paul Offit of Children’s Hospital of Philadelphia and Dr. Hank Bernstein of the Zucker School of Medicine.
Offit expressed concern about the speed of the shift, based on relatively small clinical studies. “I think as a new product it should be handled as a new product,” he said. “I think we need a higher standard than what we’ve been given. I think it’s uncomfortably scant.”
Data from both Pfizer and Moderna shows that the so-called “bivalent” vaccine produces a higher level of protection – as measured by neutralizing antibodies – compared with the existing vaccine.
While the panel didn’t vote on which omicron sub-type should be used in the vaccine, they leaned toward today’s fast-sweeping BA.4 and BA.5, rather than the original omicron BA.1.
That’s a different strategy than the one taken by the World Health Organization. Because there is so much uncertainty about the future trajectory of viral evolution, WHO is opting for a BA.1-based version, according to WHO’s Kanta Subbarao. It appears to offer a broader, rather than targeted, immune response, she said.
But the FDA panel noted that a vaccine based on the BA.4 and BA.5 subtypes seems to elicit more antibodies to those dangerous new viruses than a vaccine based on the only BA.1 version. They also protect against BA.1.
With the ancestral strain long gone, why bother including it in a new vaccine? Moderna president Stephen Hoge presented intriguing data showing that the antibody levels triggered by a bivalent vaccine stayed higher longer.
The panel also didn’t discuss whether the design of the two-dose “primary series” also should be changed. Many Americans still have not gotten these shots. According to the CDC, about 22% of eligible Americans have not received their first dose and 33% had not gotten both doses.
Even among people who are eligible for a second booster, uptake has been slow. Only about one-quarter of those over age 50 have gotten this fourth shot).
“When we started this process a couple of few months ago, we all recognized that this was an extremely complex set of issues,” said Jerry Weir, director of the FDA’s Division of Viral Products in the Office of Vaccines Research and Review.
“In spite of the complexity,” he said, “we made a lot of progress.”
