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Covid Boosters Can’t Outpace New Mutations. Here’s Why They Still Work

But over the past few months, even newer Omicron offshoots have arrived. Currently, EG.5.1, or Eris, is the dominant one in the United States, United Kingdom, and China. Meanwhile, a variant called BA.2.86, or Pirola, has been detected in several countries. Pirola has raised alarm bells because it has more than 30 new mutations compared to XBB.1.5.

Even though the new boosters were formulated against XBB.1.5, they’re still expected to provide protection against these new variants. “The reason is, while antibodies are important in protection against mild disease, the critical part of the immune response that’s important for protecting against severe disease is T cells,” says Paul Offit, a professor of vaccinology at the University of Pennsylvania and member of the FDA’s vaccine advisory committee.

These cells are a different part of the immune response. Unlike antibodies, which neutralize a pathogen by preventing it from infecting cells, T cells work by eliminating the cells that have already been invaded and boosting creation of more antibodies. Both the Moderna and Pfizer-BioNTech Covid vaccines produce long-lasting T cells in addition to antibodies.

It’s why, Offit says, when the Omicron wave hit in late 2021 and peaked in January 2022, the US didn’t see a dramatic increase in hospitalizations and deaths even as cases rose significantly: People’s T cells kicked into gear, even when their antibodies didn’t recognize the Omicron variant.

“In some ways,” says Offit, when it comes to vaccine booster development, “it almost doesn’t matter what we pick to target” because the coronavirus has yet to evolve away from T cell recognition. “Everything works.”

Scientists think T cells are able to protect against severe Covid because they’re recognizing parts of the virus that have remained unchanged throughout the pandemic. “I suspect that as we continue to vaccinate, there are some conserved regions [of the virus],” says Jacqueline Miller, Moderna’s head of infectious diseases. “So even with the accumulation of mutations, we’re still building on previous immunity.”

People who have hybrid immunity—that is, have had a Covid infection and have also been vaccinated—seem to have the best immune responses to new variants, she says, which suggests that previous exposure shapes and improves immune responses to new variants. Preliminary studies show that antibodies generated by previous infections and vaccinations should be capable of neutralizing Pirola.

Earlier this month, Moderna issued a press release saying that clinical trial data showed that its updated booster generated a strong immune response against Pirola, as well as the more prevalent Eris variant.

In a statement to WIRED, Pfizer spokesperson Jerica Pitts said the company continues to closely monitor emerging variants and conduct tests of its updated monovalent booster against them. Data presented at Tuesday’s CDC meeting showed that Pfizer-BioNTech’s updated booster elicited a strong neutralizing antibody response against both Eris and Pirola.

The FDA expects that Covid-19 vaccines will continue to be updated on an annual basis, unless a completely new variant emerges that requires a different approach. “We will always be a little behind the virus,” says Ho. “In this instance, we won’t suffer too much, but that might not be the case going forward. Surveillance is imperative.”


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