If another Covid-19 booster shot is needed this fall, it might not be the same shot you got the last time.
U.S. health officials say that coronavirus cases could pick up again in the colder months, and scientists are continuing to evaluate whether another dose will be needed.
If Pfizer-BioNTech or Moderna get their way, the next round of vaccines will contain a new formulation that targets the supercontagious omicron variant, or perhaps two strains of the coronavirus, instead of just one.
The world is going to need an updated Covid vaccine this fall, one that's “tuned to the right combination of variants,” Moderna Chief Medical Officer Dr. Paul Burton told NBC News.
Omicron-fueled Covid cases are continuing to decline in the United States and other parts of the world. Still, the coronavirus is likely here to stay, with Covid probably becoming a seasonal virus, similar to influenza, Dr. Rochelle Walensky, director of the Centers for Disease Control and Prevention, and other top health experts suggest.
Viruses can keep mutating
No one knows what the predominant circulating variant will be in the coming months, but scientists, including those at the World Health Organization, say the current vaccines may need to be updated to ensure they continue to provide a high level of protection against severe disease and death.
The existing booster shots in use, from Pfizer and Moderna, are still formulated to target the original form of the coronavirus identified in late 2019.
Moderna thinks the dominant strain this fall could be a familiar one: omicron, delta or a descendant of either of the two.
"Delta is still there and omicron is going to continue to be there as well," Burton said. "These variants are now going to go into the Southern Hemisphere, where they'll either continue to proliferate or they may mutate again."
Both Moderna and Pfizer are testing new omicron-specific shots, which have already begun trials and could be ready by the fall.
Moderna is also developing a so-called bivalent vaccine that combines an omicron-specific vaccine with the company’s original formula into a single shot. The bivalent vaccine, which the drugmaker calls its “ideal candidate” for the fall, is expected to enter human trials in “the coming weeks,” Burton said.
To be sure, there's no guarantee that any of the new vaccines under development will work as intended, said John Moore, a professor of microbiology and immunology at the Weill Cornell Medical College.
He pointed to an animal study, posted online to a preprint server in February, that suggested an omicron-specific booster shot may not provide any greater protection compared to the existing boosters. The study, from scientists at the National Institute of Allergy and Infectious Diseases, looked at blood samples from primates that had been boosted with a shot based on omicron or the original form of the coronavirus.
And the new shots may not be needed, Moore said, noting the protection provided by the existing vaccine against severe disease, hospitalization and death may still hold up. He was especially skeptical of the bivalent vaccine because, he said, throughout the Covid pandemic, there’s never been two variants dominating at the same time.
Pfizer and Moderna are "making a guess," he said, adding scientists may not know what shot will be needed for a few more months.
"This is when predicting the future becomes really, really crappy," Moore said.
Could FDA clearance happen faster?
In any scenario, Pfizer and Moderna would likely need a compelling case for why new shots are advantageous over the existing vaccines, backed up by robust safety and immunogenicity data, said Dr. Celine Gounder, an infectious disease specialist at NYU Langone Health in New York City.
"The reason why we haven't updated the vaccines is because we've seen by just giving an additional dose, you in the short term can bump up the antibody titers." she said.
The drugmakers would need to submit their data to the Food and Drug Administration for review.
The FDA has previously said modified Covid vaccines against new, emerging variants, such as omicron, may be authorized without the need for lengthy clinical trials. It's unclear if the agency would make the same exception for a bivalent vaccine.
The agency could grant an emergency use authorization for a bivalent vaccine if it thought there was a need, said Norman Baylor, president and chief executive of Biologics Consulting and a former director of the FDA’s Office of Vaccine Research and Review.
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He said he hopes federal regulators are giving the drug manufacturers instructions on what sorts of data they would need, otherwise it would be a “waste of resources if everybody’s just kind of doing clinical trials to see what sticks.”
"Both Pfizer and Moderna have licensed products, so the FDA might say, 'Let's do a noninferiority study against your licensed product,'" Baylor said. A noninferiority study looks at whether a new treatment is better or worse than the active treatment to which it is being compared.
If there's evidence of an advantage, and it's safe, it would make sense for regulators to authorize, said Dr. Jesse Goodman of Georgetown University, a former FDA vaccine chief.
A new vaccine would certainly complicate manufacturing, both Baylor and Gounder said. And the new vaccines won’t be helpful if they can’t be produced at a mass scale.
Moderna's Burton acknowledged that manufacturing a bivalent vaccine is "technically harder to do," as it involves combining two mRNAs into a single lipid nanoparticle. The company has experience with this, he said, with its mRNA-based cancer vaccine candidates that can bring together 30 different antigens into a single shot.
He said the company is confident it could make a compelling case to the FDA, using a wide range of data from its original vaccine, its omicron-specific shot and the bivalent vaccines it has already tested or will test.
Who will need another booster?
If a new booster is authorized, it's likely only some Americans would need to get the shot, said Dr. Paul Offit, a vaccine expert at Children's Hospital of Philadelphia.
Protection against severe disease, hospitalization and death provided by the first two doses of the mRNA vaccines still appear to be holding up in healthy people, he said.
Still, people living in nursing homes, the elderly, those who are immunocompromised and those with high-risk conditions may benefit from an extra dose, Offit said.
Gounder agreed that at-risk people should get the additional shot, especially if it was shown to provide broader protection. But she worried that introducing a new vaccine could further increase vaccine hesitancy among some people, especially those who are reluctant to get the shots.
Michael Osterholm, director of the University of Minnesota’s Center for Infectious Disease Research and Policy, suggested new vaccines this fall, and potentially others going forward, could be given by health care providers alongside the flu shot.
His center is working to develop a "roadmap" for a pan-coronavirus vaccine, which is expected to detail the process for research and development, financing and use of the shots.
Scientists constantly monitor influenza strains and, each year, select three to four that they think will be circulating widely to include in the flu vaccine.
Biologics Consulting's Baylor said it may be too soon to know which coronavirus variants will be dominant, but there’s growing evidence that the existing vaccines, though they still provide protection against hospitalization and death, aren’t as durable against infection from the virus. He said it may be time to update the vaccines to target the dominant variant circulating.
"It's pretty good with the original, but could it be better?" he said. "I don't know, until we see the data."