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Is a second COVID-19 booster right for me?

The FDA’s approval for a second Pfizer or Moderna booster shot took many by surprise, including many members of their own vaccine advisory committee who had expected to debate the question at a meeting on April 6. But instead of waiting for the committee to weigh in, the agency acted at the end of March, okaying a second mRNA booster, to be given at least four months after the first, for adults over 50 and severely immunocompromised individuals as young as 12. In doing so, the FDA cited a large Israeli study showing that a fourth dose of an mRNA vaccine significantly reduced both infection and severe illness in people over 60 during the recent Omicron surge.

So, if I’m more than four months out from my first booster and otherwise eligible, should I jump at the chance to get a second?

Hand holding a Magic 8-ball with the message, 'Signs point to ...'

There’s no one-size-fits-all answer, says Associate Medical Director Shawn Ferullo. “Most people will remain very well protected against serious illness after a single booster,” he notes. “Vaccine-generated antibodies don’t stick around forever. But vaccines train the immune system to recognize and fight the virus if infection occurs, even after circulating antibodies have waned. All evidence indicates that they continue to do that very well.

Indeed, even as the highly transmissible, immune-evading Omicron variant infected large numbers of vaccinated Americans earlier this year, a CDC study published at the end of last month confirmed that vaccination remained highly effective at preventing the worst outcomes. Vaccine effectiveness against death or mechanical ventilation was 79 percent for individuals who had received two doses of an mRNA vaccine and 94 percent for those who had received a booster shot as well.

But just how many boosters are we going to need? While the answer to that question is still unknown, at their meeting last week, most members of the FDA’s Vaccines and Related Biological Products Advisory Committee seemed to agree that boosting every four months was not a viable long-term strategy. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, who announced the agency’s decision to authorize second boosters at the end of March, called the shots “a stopgap measure” to provide an extra layer of protection to the most vulnerable while research continues and longer-term strategies are being considered.

Those “most vulnerable” include individuals with underlying medical conditions, about a third of all adults over 50. Healthy individuals older than 60 are also considered to be at higher risk, because they are likely to have produced a less robust immune response to previous vaccinations than younger individuals. But while the Israeli researchers found that a second booster is useful for this group, it’s important to note that this study followed these individuals for only six weeks after their second boosters. Nor were individuals randomly assigned to get a second booster or not; in other words, it’s possible that the individuals who chose to get a fourth shot were those who tended to be more cautious in general and, therefore, less likely to take risks that might have exposed them to the virus. A second Israeli study found that a fourth mRNA vaccine bolstered antibody levels in healthcare workers but was only modestly successful in preventing infections.

Okay, so SHOULD I get a booster, and, if so, WHEN?

“There’s no huge downside to getting a second booster, unless you are recently recovered from a breakthrough infection,” Ferullo says. A recent preprint study showed that vaccinated individuals who had recently recovered from a Omicron infection demonstrated strong immunity not only to Omicron and the newer Omicron subvariant BA.2, but also to earlier strains, including Delta and Beta. A peer-reviewed study in the New England Journal of Medicine also showed that vaccinated individuals who had been infected with the original Omicron strain showed neutralizing antibody responses against subvariants. “An infection acts as a kind of ‘immune boost,’” Ferullo explains, “Getting a booster shot too soon thereafter runs the risk of interrupting and restarting an immune-building process that the infection began,” he explains. “The longer those memory B and T cells have to mature, the better equipped they will be to fight a new infection, so it makes sense to delay a booster for a few months after recovery.”

Otherwise, if you are eligible and tolerated previous shots well, a second booster won’t hurt, says Ferullo. While some news articles have floated the idea that repeated boosters could lead to “immune exhaustion” like that seen in HIV or hepatitis C, in which T-cell immune response weakens after trying and failing to fight off an antigen for years on end, Ferullo dismisses this concern. “Since the proteins elicited by mRNA vaccines have a lifetime of just a few days, you’d have to give boosters weekly over a long period of time to exhaust your T cells,” he says.

But while a second booster is likely to raise antibody levels and bolster protection against infection, we don’t know the extent of that increased protection or how long it lasts. “There should be additional data out of Israel soon, and that could tell us more, but for now it’s a question of trying to time the shot to have the highest level of protection when you need it most,” Ferullo says. “It’s fine to wait if your risk of exposure is low right now. You might want to keep an eye on the wastewater data for your area — that’s probably the best current indicator of community spread. You might also want to time your booster around travel or other plans that could increase your risk of exposure.”

The lack of explicit guidance can be frustrating, Medical Director Cecilia Stuopis acknowledges. “But living with this virus is going to mean living with some uncertainty, some amount of risk, and a whole lot of individual responsibility,” she says. “Your primary care provider can offer guidance, but in the end, when it comes to boosters, masking, and other precautions, we each need to consider our individual circumstances and make the decisions that work for us.”

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