Companies need several months to manufacture a new vaccine, so the deadline to choose a vaccine formula to be ready to roll out in October has arrived. The FDA is expected to issue a final decision in the coming days.
But no one knows what variants will be circulating this winter, and it is reasonable to expect that any omicron variant incorporated into the updated vaccine will be in the rearview mirror by the time shots are going into arms. Updated vaccines that include BA.1 have been in human tests for months, but that variant circulated this winter and has already been eclipsed by other versions of omicron; the subvariants BA.4 and BA.5 already make up half of the cases in the United States.
There is also uncertainty about whether updated vaccines will really protect people better. Companies showed they were able to trigger modestly higher levels of virus-blocking antibodies, but it remains unknown whether that will translate into better protection against hospitalization or infection. The hope is that a revamped vaccine will broaden the immune response.
“We’re being asked, more or less, to have a crystal ball today,” said Arnold Monto, acting chairman of the FDA advisory committee and an emeritus professor of public health at the University of Michigan School of Public Health.
In discussion, many members of the committee said the vaccine should be a multi-strain vaccine that includes the original version of the virus and a component of omicron. Many members and FDA officials favored the BA.4 and BA.5 omicron subvariants, but some saw promise in including the BA.1 version of omicron.
“I think given the speed of evolution [of the virus] we’re going to be behind the eight ball if we wait longer,” said Mark Sawyer, a professor of clinical pediatrics at the University of California San Diego School of Medicine. “Public perception is that FDA is already delaying approvals. I think we have enough data here presented today to move forward with a strain change.”
Vaccine companies, including Moderna, Novavax, Pfizer and its German partner BioNTech, presented sometimes conflicting data on potential booster strategies, leaving committee members to triangulate between overlapping, sometimes divergent results.
Paul Offit, a vaccine expert at Children’s Hospital of Philadelphia, called the data “uncomfortably scant” and voted against changing the strain. He questioned whether the modest difference in how modified vaccines triggered an immune response was a big enough difference to translate into a benefit for people.
“I don’t think it’s fair to ask people to take a risk … if we don’t feel comfortable with the level of protection that we’re likely to get,” Offit said.
The companies each presented data to support their preferred strategy.
Moderna, for example, favors a bivalent vaccine tailored to protect against the original version of the virus and the omicron BA.1 variant. The company said it could start delivering the vaccine this summer, but cautioned that a vaccine that includes BA.4 and BA.5 could take until late October or early November.
Pfizer and its German partner BioNTech, however, found that a vaccine that targets a single variant of the virus, BA.1, was better than a bivalent formulation. The company also presented mouse data suggesting that a vaccine tailored to fight the omicron subvariants that are projected to soon dominate in the United States, BA.4 and BA.5, might provoke stronger and broader immune responses. The company would be ready to supply either version of the vaccine by the first week of October.
Novavax’s vaccine has not yet been authorized in the United States, but uses a different technology — delivering a viral protein brewed in a laboratory. The company presented data suggesting that additional doses of its existing vaccine could be protective, even against omicron subvariants. Clinical testing of its omicron booster is ongoing, with results expected in September.
Adam Berger, director of the division of Clinical and Healthcare Research Policy at the National Institutes of Health, said that the data presented at the meeting suggest that while a universal recommendation to change vaccines is preferred for simplicity, the array of results suggest “there isn’t a one-size-fits-all answer to whether a strain change is necessary.”
Several experts raised the concern that if the United States switched its vaccine composition, it could exacerbate global vaccine equity issues and perceptions of vaccines. It also was unclear whether a vaccine change would apply to adults or also include children. Several experts said that if the vaccine is changed for children, they would like to see more testing.
But during the public comment session, several parents made impassioned pleas that the vaccines be updated for all age groups, including the youngest children.
The wait for vaccines for children under 5 was “long and excruciating,” said Kate Schenk, a mother of three children. “We cannot let this happen again. Children need to be eligible to receive these updated boosters alongside older cohorts — not lagging behind, unprotected.”
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research pointed out that half of Americans haven’t received a booster, despite clear evidence that a third shot re-ups and broadens protection. Even those who have received boosters will become vulnerable again over time as immunity wanes.
“The better the match of the vaccines to the circulating strain, we believe may correspond to improved vaccine effectiveness and potentially to a better durability of protection,” Marks said.
But even an updated vaccine won’t reset the pandemic and provide perfect protection against a rapidly evolving and highly transmissible virus. The omicron subvariants that are already growing in frequency today are not likely to be the ones that the world faces in the fall. How well vaccines based on them will protect against the future iterations of the virus won’t be fully known until they’re being used.
The process has been compared to picking the flu vaccine each year. Some years, it is a better match to the flu strains that circulate than others.
But flu is a different virus, and the meeting is an early step in the long-term challenge of trying to craft a vaccination strategy.
“I will remind you that the parallel track of influenza strains selection, which works very well, was a process that was honed over many, many years. And so we probably have quite a bit of work,” said Jerry Weir, director of the Division of Viral Products in the Office of Vaccines Research and Review. “This is a different virus. We have a lot of work to do on the strain selection process for covid vaccines.”