Focused on warding off a cold-weather surge of coronavirus infections and on revamping the COVID-19 vaccine response, health experts approved a new and likely improved version of the vaccine for the first time since the virus emerged.
Following the Food and Drug Administration’s Aug. 31 recommendation, the Centers for Disease Control and Prevention signed off on the first-ever variant-specific booster on Sept. 1, just in time for the Labor Day weekend’s ushering in of fall.
The double-edged vaccine targets both the original virus strain and its BA.4 and BA.5 descendants, responsible for nearly all COVID-related infections today. Health officials expect the bivalent vaccine will curb infection rates before respiratory illness season peaks, generally in the winter months.
Officials gave the greenlight despite some expressed concern over lack of human clinical trial data, predicting the timely move could prevent 137,000 hospitalizations and 9,700 deaths. Moreover, many experts say, the accelerated approval puts the country on track to keep up with the virus, which has been evolving at a sprinter’s pace.
“In order to stay current with whatever strains are out there, we are going to have to move this much more quickly than we can possibly do with clinical trials,” said Ross Kedl, PhD, professor of Immunology & Microbiology at the University of Colorado School of Medicine (SOM). “I believe this is the absolute correct way of doing it.”
Adequate data for approval questioned
Largely because the FDA asked manufacturers to halt studies in June looking at a BA.1-specific vaccine and to quickly pivot to creating a BA.4/BA.5 version instead, data reviewed for the new booster’s approval came from animal studies and a small clinical trial on the BA.1 vaccine.
But some experts – including Paul Offit, MD, of the FDA’s advisory committee and Thomas Campbell, MD, CU SOM professor of Infectious Disease – questioned authorizing a national immunization campaign based largely on mice studies against a novel virus. Whether the new boosters are indeed effective at blocking BA.4/BA.5 infections, while likely, remains uncertain.
The new formulation triggered antibody responses in mice against the circulating strains at acceptable levels, Campbell said. “But what we don’t know is whether that translates to similar levels of antibodies in humans, and we don’t know if that translates to protection against infection in humans. So those are the data that we’re missing.”
Officials are extrapolating from those mice studies and the human studies of a bivalent BA.1 vaccine in fewer than 1,400 people in predicting the efficacy and safety of the vaccines, said Campbell, who has led COVID-19 vaccine clinical trials at the CU Anschutz Medical Campus since early in the pandemic.
“In order to stay current with whatever strains are out there, we are going to have to move this much more quickly than we can possibly do with clinical trials.” – Ross Kedl, PhD
Mice data don’t always translate into humans, although they did with the original vaccines, he said. “I would prefer to have some in-human data before launching a big vaccine campaign with this new BA.4/5 variant vaccine,” said Campbell, adding that he would have delayed approval and continued using the original booster until more data were available.
Human clinical trials are ongoing with the new bivalent BA.4/5 vaccine, with initial data expected in about two months.
Move focused on keeping up with virus
The method used to approve the new vaccine mirrors the process used every year for the flu shot, created and approved rapidly in time for the upcoming influenza season, said Brian Montague, DO, associate professor of Infectious Disease. “Each year, they come up with vaccines for the strains that they think are going to be circulating, and then they come up with a vaccine formulation for those strains,” he said.
Human clinical trials are not performed for each new flu vaccine. If they were required, there would be no influenza vaccine campaign, Kedl said. “It would negate the usefulness of it,” he said, adding that the same strategy now makes sense for COVID-19 boosters.
“That is true that we do this with the flu vaccine every year,” Campbell said. “But we know that it works and it’s safe to do that with the flu vaccine, because we’ve been doing that with the flu vaccine for many decades. We don’t have the experience of doing that with SARS-CoV-2. And we expect that it will be similar results both for safety and effectiveness, but we just don’t know that.”
Most concern raised was with efficacy, not safety of the bivalent vaccine, Kedl and Montague emphasized. And it’s important to remember that half of the new vaccine formula contains the original virus sequence, still highly effective against severe disease and death.
“The worst-case scenario is that it’s less effective than we think against BA.4 and BA.5,” Montague said.
“That is true that we do this with the flu vaccine every year. But we know that it works and it’s safe to do that with the flu vaccine, because we’ve been doing that with the flu vaccine for many decades.” – Thomas Campbell, MD
“Adding the BA.4/BA.5 sequence is going to have no impact on what we already know is a remarkably safe and stable vaccine,” Kedl said. “We have just spent the last three years testing this vaccine and implementing this vaccine in billions of people across the globe. The only thing that has changed is a little bit of the mRNA sequence to adapt it to the most recent viral strains, again, exactly like we do for influenza.”
Lowering risk, protecting community
Elevating immunity against specific variants has a better chance of blocking infection, ultimately protecting against even a new variant that might emerge, Kedl said. “If we can stop reinfections from happening at a significant enough rate, we might slow the rate new variants spin out.”
Remembering the big picture as COVID-19 has gotten milder is important, Montague said. “I think we sometimes think of it and the decision about getting a vaccine as, ‘Well, I’m probably not going to get all that sick. It doesn’t really matter.’”
But it does matter, Montague said, pointing to a significant immune-compromised population that exists that could become gravely ill from a person’s mild breakthrough infection. “You wouldn’t know when you saw them, but you might interact with them and pass the virus on. I think it’s important to protect the people around you and to lower the risk of new circulating strains for the community.”
New COVID-19 Booster: What You Need to Know
Who can get the Moderna bivalent vaccine? Anyone 18 and older who has had the original series.
Who can get the Pfizer bivalent vaccine? Anyone 12 and older who has had the original series.
Who is eligible? Everyone in the approved age group who has had the original COVID-19 vaccine series, including the Johnson & Johnson/Janssen and Novavax vaccines.
When and where are they available? Vaccines should begin arriving after Labor Day at the regular health sites and pharmacies that have been giving COVID-19 shots.
What about children under 12? The original, monovalent booster schedule remains the same. Both mRNA manufacturers are proceeding with variant-specific vaccines and clinical trials in the younger age groups.
How long should I wait after a previous booster shot or omicron illness? At least two months after the last vaccine and three months post-infection. Stretching the wait out to three to five months to optimize length of immunity is acceptable for non-high-risk people.
Can I still get the original monovalent booster? No. The monovalent booster is no longer available for anyone eligible for the bivalent booster.
Can I get a flu shot with the new booster? Yes. Studies show COVID and flu shots are as effective given in combination as opposed to separately. And bonus: Combining means only one bout of the vaccine side effects (fatigue, soreness, fever) instead of two.