- Experts began discussions on when and how to update existing COVID-19 vaccines and when to offer additional boosters.
- No decision was made on whether boosters will be recommended in the fall, similar to how flu shots are recommended to the general public on an annual basis.
- The meeting comes after the FDA authorized people over 50 to get a second booster dose.
The Food and Drug Administration’s (FDA) vaccine advisory panel met Wednesday to discuss future COVID-19 booster doses and how to prepare for new strains of the coronavirus that may emerge.
No decision was made at the meeting on whether boosters will be recommended in the fall in preparation for a potential winter surge. A follow-up meeting is expected by early summer for further discussions.
During the meeting, experts outlined the challenges in staying ahead of a virus that has evolved into multiple variants, some highly transmissible and others capable of overcoming the immune protection produced by both vaccines and prior infection.
This meeting comes after the FDA authorized second booster doses for adults over age 50 and certain people with weakened immune systems, and as the agency is set to consider COVID-19 vaccines for very young children.
All viruses can mutate and give rise to new strains, but they do so at different rates. SARS-CoV-2, the coronavirus that causes COVID-19, has been especially adept at this process.
During the advisory committee meeting, Trevor Bedford, PhD, a researcher at the Fred Hutchinson Cancer Center in Seattle, said that in terms of evolution, the coronavirus has accomplished in two years the equivalent of five years of seasonal flu evolution.
Since SARS-CoV-2 first emerged in late 2019, it has evolved into multiple variants, including variants of interest (VOIs) and the more serious variants of concern (VOCs).
Some of the more transmissible variants, such as Delta and Omicron, have swept through the population, rapidly displacing existing strains. Others, such as Beta, have shown the ability to evade vaccine- or infection-acquired immunity.
However, even after two years of studying SARS-CoV-2, scientists are hesitant to predict what will come next with the coronavirus.
“Exactly assessing the probabilities here is quite difficult,” said Bedford.
He offered two possible scenarios — a slightly different variant could develop from one of the currently circulating ones, or a variant with many mutations could come out of nowhere, as did Omicron.
The first situation is similar to how the seasonal influenza virus evolves — incrementally.
Bedford said it’s more likely that new strains will develop from one of the Omicron sublineages currently circulating. However, he added that a vastly different coronavirus variant could appear every 1.5 to 10.5 years.
Scientists can use blood from people who have been vaccinated to see if an existing vaccine is likely to work against a variant. This method would work for a variant that has already been identified.
But to stay ahead of the ever-evolving coronavirus, it would be helpful to have a way to predict whether a vaccine would work against new variants that have yet to emerge.
During the meeting, Dr. John Beigel, associate director for clinical research in the National Institute of Allergy and Infectious Diseases (NIAID) Division of Microbiology and Infectious Diseases, described research to allow scientists to do just that.
“Until we know more [about how the virus will evolve], we have to know how to react to a new strain that may arise,” he said.
The current COVID-19 vaccines are based on the original strain of the virus. But the vaccines also work against all of the variants that have arisen — to varying degrees.
The NIAID is running a clinical trial in which people will be given a COVID-19 vaccine based on the original strain of the coronavirus or other known variants. Some people will also receive a booster.
Scientists will measure how well the antibodies in the blood of those people work against the existing variants.
They can predict how well the vaccines or vaccine-booster combinations might work against new variants that might arise, based on how similar those potential variants are to existing ones.
This work is based on the ability of antibodies produced in response to vaccination to target a variant. However, antibodies are just one part of the immune response.
Panel member Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, suggested that measures of T cells might provide a better idea of how well the vaccines might work against a new variant, in particular the protection offered against severe illness.
Seasonal flu vaccines are updated each year based on scientists’ predictions of which flu viruses will be circulating that year. This experience may be useful in guiding updates to the COVID-19 vaccines.
However, the flu season is very regular, making it easier for scientists to make predictions. The same may not be true of the coronavirus.
“I’m not sure the data supports seasonality for COVID-19. We may be on a different timeline [than for flu],” said Adam Berger, PhD, director of Clinical and Healthcare Research Policy at the National Institutes of Health.
In addition, there are many different platforms for the COVID-19 vaccines, including mRNA, adenovirus, and protein subunit. These technologies complicate the vaccine update process.
Another challenge of updating the COVID-19 vaccines is manufacturing capacity. Even if a vaccine had high efficacy against a new variant, if vaccine makers couldn’t make enough doses, this vaccine would do little to help the world.
Berger also raised the question of whether manufacturers would be able to produce enough doses of the existing vaccines while also producing prototype vaccines for testing against new variants.
One of the advantages of the mRNA vaccines, though, is that they can be rapidly redesigned. However, designing the vaccine and producing enough doses are separate problems to be solved.
One of the challenges outlined during the meeting is knowing when to update the existing vaccines to target a new variant or possibly to target multiple variants.
Before a new vaccine can be rolled out to the public, the FDA requires clinical trials to be done. This takes time.
Panel member Dr. Michael Nelson, a professor of medicine at UVA Health, said if clinical trials had been started shortly after the arrival of the Omicron variant, by the time the clinical trials were done, the wave would have passed.
This approach risks not only missing the current wave, he said, but also having a vaccine that doesn’t protect against a future variant.
Another way to think about whether to modify the existing vaccines is to look at how well they are working against the existing variants in circulation.
Or, as panel member Dr. Cody Meissner, a pediatrician at Tufts University School of Medicine, put it: “At what point will we say the vaccine isn’t working well enough?”
This can be done by testing the blood of vaccinated people to see how well antibodies in their blood recognize and neutralize a particular variant.
Many studies have done this kind of analysis. However, scientists don’t yet have a clear sense of how much neutralizing activity is “enough.” This is also known as the “correlates of protection.”
In addition, while the level of antibody activity can give a good sense of how well a vaccine may protect against infection, it may not predict how well it protects people against severe illness.
For that, scientists turn to data from real-world vaccine effectiveness studies.
Current studies show that three doses of the existing mRNA COVID-19 vaccines continue to offer strong protection against severe illness, hospitalization and death.
So the question that would need to be decided is how low does this protection have to drop in order for vaccines to need to be modified.
If there is a drop in protection, boosters with the existing vaccines can restore some of the immune protection against both infection and severe illness.
However, Dr. Amanda Cohn, director of the CDC’s Division of Birth Defects and Infant Disorders, said boosting everyone every few months is not a long-term strategy. So she asked what level of protection will panel members be comfortable with?
“Given that our effectiveness against hospitalization in immunocompetent individuals is over 80 percent, and that’s in older adults and in persons with chronic medical conditions, I think we may have to accept that level of protection, and then use other alternative ways to protect individuals with therapeutics and other measures,” she said.
This question was discussed at the meeting, but panel members made no decision.
The advisory group is expected to meet again, likely by early summer, said Dr. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.
During that meeting, panel members will review additional clinical and laboratory studies data that might help guide their decisions.
They will also discuss whether additional boosters should be offered in the fall before a possible winter surge and the framework needed for deciding when and how to update the existing vaccines.