It takes companies several months to produce a new vaccine, so the deadline has passed to select a vaccine formula, which should be ready for launch in October. The FDA’s final decision is expected in the coming days.
But no one knows what variants will be in circulation this winter, and it’s reasonable to expect that every Omicron variant integrated into the updated vaccine will be in the rearview mirror when the gunshots go. Updated vaccines containing BA.1 have been in human testing for months, but this variant circulated this winter and has already been eclipsed by other versions of Omicron; subvariants BA.4 and BA.5 already account for half of cases in the United States.
There is also uncertainty as to whether updated vaccines will really protect people better. The companies showed they were able to elicit slightly higher levels of virus-blocking antibodies, but it remains unknown if this will translate to better protection against hospitalization or infection. The hope is that a revised vaccine will broaden the immune response.
“We’re kind of being asked a crystal ball today,” said Arnold Monto, acting chair of the FDA Advisory Committee and professor emeritus of public health at the University of Michigan School of Public Health.
During the discussion, many members of the committee said that the vaccine should be a multi-strain vaccine containing the original version of the virus and a component of Omicron. Many members and FDA officials preferred the Omicron subvariants BA.4 and BA.5, but some saw promise in including the BA.1 version of Omicron.
“I think given the speed of evolution [of the virus] If we wait any longer, we will lag behind,” said Mark Sawyer, professor of clinical pediatrics at the University of California School of Medicine at San Diego. “The public perception is that the FDA is already delaying approvals. I think we have presented enough data here today to move forward with a strain change.”
Vaccine companies, including Moderna, Novavax, Pfizer and its German partner BioNTech, presented sometimes conflicting data on possible booster strategies, leaving panel members to triangulate between overlapping, sometimes divergent, findings.
Paul Offit, a vaccines expert at Children’s Hospital of Philadelphia, called the data “uncomfortably sparse” and voted against changing the strain. He questioned whether the subtle difference in how modified vaccines elicited an immune response was big enough to translate into a benefit for people.
“I don’t think it’s fair to ask people to take a risk… when we’re not comfortable with the level of protection that we’re likely to receive,” Offit said.
The companies each provided data to support their preferred strategy.
For example, Moderna 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 shipping the vaccine this summer but warned that a vaccine containing BA.4 and BA.5 could take until late October or early November.
However, Pfizer and its German partner BioNTech found that a vaccine targeting a single variant of the virus, BA.1, performed better than a bivalent formulation. The company also presented mouse data suggesting that a vaccine tailored to combat Omicron subvariants BA.4 and BA.5, which are expected to soon dominate in the United States, could elicit stronger and broader immune responses. The company would be ready to deliver both versions of the vaccine by the first week of October.
Novavax’s vaccine has not yet been approved in the United States, but it uses a different technology — delivering a viral protein brewed in a lab. The company presented data suggesting that additional doses of its existing vaccine could even protect 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 Medical Research Policy at the National Institutes of Health, said the data presented at the meeting suggests that while a general recommendation to switch vaccines is preferred for simplicity, the range of results is suggesting that “there is no such thing as a universal answer as to whether a strain change is necessary.”
Several experts expressed concern that changing vaccine composition in the United States could exacerbate global vaccine equity issues and vaccine perceptions. It was also unclear whether a vaccination change would apply to adults or children as well. Several experts said they would like to see more testing if the vaccine for children is changed.
But during the public comment session, several parents made a passionate plea for vaccines to be updated for all ages, including the youngest children.
The wait for vaccines for children under five is “long and agonizing,” said Kate Schenk, a mother of three. “We can’t allow that to happen again. Children must 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 have not received a booster shot, despite clear evidence that a third shot increases and extends protection. Even those who have received booster shots become vulnerable again over time as immunity wanes.
“We believe that the better the vaccines’ match to the circulating strain may correspond to improved vaccine efficacy and potentially better durability of protection,” Marks said.
But even an updated vaccine will not reset the pandemic and will provide perfect protection against a rapidly evolving and highly transmissible virus. The Omicron subvariants, which are already increasing in frequency today, probably won’t be the ones the world will face in the fall. How well vaccines based on it will protect against future iterations of the virus will not be fully known until they are used.
The process was compared to annual flu vaccine selection. Some years it fits the circulating flu strains better than others.
But the flu is a different virus, and the meeting is an early step in the long-term challenge of developing a vaccination strategy.
“Let me remind you that the parallel selection of the influenza strains, which works very well, was a process that was refined over many, many years. And that’s probably why we have quite a lot of work to do,” said Jerry Weir, director of the viral products division at the Office of Vaccines Research and Review. “It’s a different virus. We still have a lot of work to do in the strain selection process for Covid vaccines.”