A mix-and-match Covid-19 booster vaccine policy would provide two distinct advantages: a stronger immune response to the extra shot, plus a lot less confusion for people seeking booster doses.
Early results from research being done by a National Institutes of Health-led team shows that giving people a different type of booster shot from their original vaccine type provided a stronger immune response than giving an extra dose of the same vaccine – findings in line with research done earlier in the year in Britain.
It’s no surprise to vaccine experts that it’s safe to mix vaccine types. People do that regularly with a variety of vaccines, including influenza vaccines, which are made by six or seven different companies in the United States alone in any given year, following a variety of formulas. They include vaccines made in chicken eggs, caterpillar cells and dog kidney cells, vaccines that protect against either three or four different influenza strains and vaccines delivered by injection or via nasal spray.
In many countries, children are given polio vaccines first as a shot and then boosted with a different, oral formulation – a combination that’s both safer and more effective.
The Pfizer and Moderna vaccines are both mRNA vaccines, made using genetic material called messenger RNA wrapped in lipids to instruct the body’s cells to make little pieces of coronavirus to stimulate an immune response. Johnson & Johnson’s Janssen vaccine uses a different method: a genetically engineered common cold virus called an adenovirus that cannot itself replicate, but that can deliver a small piece of coronavirus to cells and also stimulate an immune response.
AstraZeneca’s vaccine uses technology similar to Johnson & Johnson’s, and several studies have shown alternating doses of this vaccine with Pfizer’s generates a strong immune response.
Broader immune reponses
Mixing different vaccine types might broaden the type of immune response, said Dr. Angela Branche, an assistant professor at the University of Rochester School of Medicine who is helping run some of the clinical trials mixing booster doses.
A vector vaccine, like the Janssen or AstraZeneca vaccine, stimulates strong cellular immunity, she said. The mRNA vaccines stimulate powerful surges of antibodies. Mixing the two, she said, “can broaden the depth of the immunological response.”
“I think the data will show that boosting is certainly likely to be very effective in conferring additional and longer protection,” she told CNN. “We’ll be able to boost with all the vaccines.”
Last week, Dr. Kirsten Lyke, a professor of medicine at the University of Maryland, presented what the NIH team has found so far to vaccine advisers to the US Food and Drug Administration. The FDA asked them to weigh in on the question of mix and match boosters and is preparing emergency use authorization language for boosters that may incorporate their thoughts.
While Lyke stressed that the data was incomplete, she did say it showed boosting with a different type of vaccine from the original dose provided a stronger antibody response than did boosting with the same type.
“What I would note is that the neutralizing antibodies did increase in response to any boost of the primary vaccination series,” she told the FDA’s Vaccines and Related Biological Products Advisory Committee. “The study was not designed to compare between boosts,” she added – in other words, it could not tell people which particular brand might be best to boost with.
But that might not matter, because the other advantage of allowing people to boost with any of the three authorized vaccines in the US would be flexibility.
Messy messaging around boosters
Right now, the permission for boosters is complicated. Pfizer has emergency use authorization for a booster shot for people who are at least six months out from their fist two doses who are also 65 or older, or who are 18 and older and who are also at risk of severe disease because of an underlying condition or because their living or working conditions put them at risk.
Moderna and Johnson & Johnson have asked permission for boosters, too. Moderna’s ask mirrors Pfizer’s almost exactly, but Johnson & Johnson is asking for boosters for everyone 18 and older who got its vaccine. If FDA grants those requests, members of VRBPAC said, people will be confused.
“Now you have set up the possibility of mixing, matching and different groups being eligible,” Dr. Jeannette Lee, a professor of biostatistics at the University of Arkansas, told Friday’s meeting.
“This is going to be very, very messy in terms of the messaging.”
Dr. Amanda Cohn, an official at the US Centers for Disease Control and Prevention who sits both on VRBPAC and on the CDC’s vaccine advisory committee, said it would be very helpful if there could be flexibility for people trying to deliver boosters – for instance, for drug retailers going into nursing homes with only one brand of vaccine.
Plus, there’s the issue of people who forgot which vaccine they got or who lost their records, noted Dr. Melinda Wharton, CDC’s associate director for vaccine policy.
What might happen next?
Dr. Peter Marks, who heads the FDA’s vaccine arm, the Center for Biologics Evaluation and Research, dropped some heavy hints about the direction the agency might take.
“I think we got what we needed from this discussion,” he said. “It does seem like there is some consensus that this is an important option for people to have,” he added. “Some feel like this is enough data.”
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He noted that several members of VRBPAC said they would feel comfortable with allowing anyone over 40 to get boosters. The risk of complications from an inflammatory heart condition called myocarditis fall off considerably after age 40, he said.
That points to the possibility of FDA emergency use authorizations for boosters covering all three vaccines. CDC vaccine advisers, the Advisory Committee on Immunization Practices, meet Thursday to provide guidance on delivering boosters.
ACIP and the CDC may narrow the FDA’s parameters in giving the final word on boosters, but may not broaden them.