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U.S. to Study Mix-and-Match Scenarios for Vaccine Booster Shots

April 22, 2021, 4:31 PM

Fully vaccinated Americans may know in the coming months whether they can mix and match follow-up shots, if variants in the virus that causes Covid-19 make those boosters necessary.

The National Institute of Allergy and Infectious Diseases is planning a study to determine what happens if someone receives one type of authorized Covid-19 vaccine, say Moderna Inc.'s jab, and is boosted with another like the Pfizer Inc. or Johnson & Johnson shot.

Emily Erbelding, director of the NIAID’s division of microbiology and infectious diseases, said the institute aims to have data in hand before the fall, which means studies would have to begin in the next month or two. “People are writing protocols right now. And people are talking to regulators about them. And this is an active area of development for us,” Erbelding said in an interview.

Pfizer, Inc. and Moderna, Inc. have already begun testing booster shots for variants. Pfizer CEO Albert Bourla recently said people will likely need a booster within 12 months of being fully vaccinated and may need annual boosters. Those comments are in line with plans announced by Pfizer in February to study a third dose of the vaccine, the company told Bloomberg Law.

It’s not clear that Covid-19 boosters will be needed at all. Those follow-up shots are for patients who have received their full dosing of their initial vaccine—one or two doses, depending on the brand—whose immune systems may need an additional nudge down the road to combat variants or bolster dwindling antibodies.

If follow-up vaccinations are recommended, the National Institutes of Health study plans indicate people shouldn’t assume they’re married to a single vaccine manufacturer for life. Researchers say the booster/annual model will probably resemble the seasonal flu shot, in which several types are available each year, and people don’t usually know or care which one they get.

A key difference is that Covid-19 vaccines are less than a year old, in contrast to influenza vaccines that have been available since the 1930s. Flu shots come with decades of safety data. Covid vaccine safety data is still in its infancy by comparison.

Variant Risk

Plans for the mixed-shot study come as the emergence of several mutations of SARS-Cov-2 have made the virus more contagious, fueling new outbreaks. At the same time, vaccinations have ramped up as 200 million shots have been given as of Thursday, surpassing a goal set by the Biden administration.

One way to set up a clinical trial would be to have five or six study arms that would look at the effectiveness of different scenarios, such as giving patients who got a Pfizer or Moderna vaccine a booster of Johnson & Johnson, Erbelding said. Researchers could then compare the antibody response with participants who got both their prime vaccine and their booster from the same manufacturer.

The one-dose J&J shot is currently on pause in the U.S. due to rare instances of blood clotting in some women who received the jab, but the Centers for Disease Control and Prevention’s advisory panel for vaccine use meets Friday to discuss new safety precautions. The EU regulator resumed use of J&J April 20, saying the benefits outweigh the risk of blood clots.

Vaccines authorized in the U.S. appear to work against the variants, although the B.351 variant first identified in South Africa appears to lessen the effectiveness somewhat.

“We are taking the next steps because we need to proactively address this,” Pfizer said in a statement.

Slower Mutation Rate

Slower emergence of SARS-Cov-2 variants could make boosters unnecessary, according to San Francisco-based infectious diseases physician Monica Gandhi. If they are, she said it likely won’t matter which booster you get.

The virus that causes Covid-19 mutates more slowly compared to influenza, in part because SARS-Cov-2 has a “proofreading mechanism” that fixes “mistakes” when it makes copies of itself, according to the World Health Organization. “So it’s not like this is going to mutate like crazy every year, like the influenza virus,” she said. The vaccines are also so effective—from 70% to 95% in initial clinical trials—the level of infection in the community should drop to low levels as vaccinations ramp up.

“I do believe we’re going to reach herd immunity. I don’t think there’s even a doubt about that, given how effective these vaccines are. And so why would we need boosters for infection that’s at a very low level?” Gandhi, who’s associate division chief in HIV, infectious diseases, and global Medicine at the University of California, San Francisco General Hospital, said in an interview.

“I can’t imagine that that would be the case,” Kathryn M. Edwards, a pediatrician and scientific director of the Vanderbilt Vaccine Research Program, said of the need for an annual Covid-19 vaccine shot.

But there may be a need to update the vaccine every three or four years, and there’s already a lot of experience at the Food and Drug Administration in making those changes.

“Those things will all be pretty easy to implement because we have a lot of experience, but I think it’s just I’d take some more information before we know all those answers,” Edwards, who’s also a fellow at the Infectious Diseases Society of America, said in an interview.

It’s too early to tell whether it’s OK to mix and match prime and booster shots without the study the NIAID is planning, both Edwards and her colleague William Schaffner said.

“None of this is on the books yet. It’s not even in the display case,” Schaffner, a professor of preventive medicine and infectious diseases at the Vanderbilt University School of Medicine in Nashville, Tenn., said in a separate interview.

“I would think that you could get that so-called booster by any of the two mRNA vaccines,” Schaffner said, referring to the platform used by both the Pfizer and Moderna shots. But introducing another platform, such as Johnson & Johnson, would really need to be studied, since that vaccine is made “in a quite different way.”

Both the mRNA and adenovirus vaccines like the J&J shot target the spike protein that the novel coronavirus uses to infect human cells, Edwards noted.

Variety May Be Better

There’s some evidence in other viruses such as Ebola that using two different vaccine platforms can increase the antibody and T-cell response, Erbelding said. “That’s a concept that we’re trying to think through right now. And we’d like to use the tools that we already have in our toolbox, rather than developing a different variant vaccine every single year.”

Gandhi said it probably wouldn’t matter which brand of shot patients receive in the future to fight off Covid variants.

“All I do is give out vaccines to people over a long career. And we never check the brand,” Gandhi said. When patients need boosters for hepatitis B or hepatitis A shots, for example, providers use just whatever vaccine with which the hospital has contracted. “I don’t think in the future, it’s going to matter,” she said.

In addition to researching and developing booster shots, curbing the rise of mutations in the first place is critical to ending the pandemic, Edwards said. “Then there’s going to be less virus growing, and there’s less opportunity for variants to arise.”

To contact the reporter on this story: Jeannie Baumann in Washington at

To contact the editors responsible for this story: Fawn Johnson at; Alexis Kramer at

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