It feels intuitively right that a reformulated booster vaccine aimed at the omicron BA.5 variant would vastly improve our protection against it as well as any offspring that might threaten us in the fall. But intuition doesn’t always agree with scientific data.
It’s not intuitive at all to think that waiting six months before getting boosted vastly improves protection. Yet that’s what the data show, and it’s starting to make sense to a few researchers who are looking under the hood at how our immune systems work and what they’re capable of, given enough time.
There’s almost no public data on the efficacy of the boosters for the currently circulating omicron BA.5. Yet the Joe Biden administration has purchased more than 170 million doses from Pfizer-BioNTech and Moderna. Pending recommendation from the Centers for Disease Control, the shots will be available to all adults who are fully vaccinated and, for the Pfizer, to teens as well.
“We have no clinical data, not even neutralizing antibody data in people,” said Paul Offit, a pediatrician at the Children’s Hospital of Philadelphia and a member of the Food and Drug Administration’s advisory committee on vaccines. “There’s a mouse study but nobody has seen it.”
Scientists did gather some data on the potential efficacy of a booster aimed at an earlier version of omicron, BA.1, by measuring how well antibodies in blood samples from volunteers attacked the virus. They found that including a BA.1 component offered only a modest improvement over the original boosters. The difference, Offit said, was comparable to the differences between the Pfizer and Moderna shots — a difference he says is not clinically significant.
The new formulation uses the same mRNA technology as the original shots, but includes new genetic material corresponding to two closely related variants, BA.4 and BA.5. The new shot is very unlikely to pose any new health threat, but if it’s no better than the original, it represents a waste of resources, said John P. Moore, a virologist at Weill Cornell Medicine. Most of the people who are hospitalized and dying are unvaccinated or have skipped the initial booster, he said.
The one group for whom the new formula should matter are the completely unvaccinated — but they are, inexplicably, not eligible for it. Instead, any holdouts who finally decided to get vaccinated would have to get the original shots first. “I don’t understand that at all,” Moore said.
Offit warns that modeling the Covid vaccination campaign after the flu is a mistake. Flu viruses mutate in a way that can render the previous year’s shots completely ineffective, but this is not the case at all for SARs-CoV-2. That’s why those who just had a booster last summer shouldn’t fret. We can wait a few more months without fear we’re missing a major upgrade.
Scientists have two ways of thinking about the similar performance of the new and old formulations. One is a phenomenon that’s come to be called immune imprinting. The idea is that the immune system gets stuck focused on the original target of the vaccine and can’t adapt well to a new shot. Scientists admit they don’t have a very good understanding of why it happens or how much it matters for Covid vaccines.
Immunologist Duane Wesemann says a better explanation for the similar performances of new and old vaccines is more of a glass half-full idea. The original vaccines work surprisingly well against the new variants if given enough time. Time is the key.
Wesemann, who heads a lab associated with Harvard Medical School and Brigham and Women’s Hospital in Boston, looked into the effects of time after puzzling over results of some experiments done right after the omicron variant started spreading late last fall. Back then, scientists warned that antibodies from the blood of fully vaccinated people had almost no power to disable the omicron variant, but antibodies from people who’d been boosted after a period of six months did so reasonably well.
Why, he wondered, would giving an additional dose of something that acted so weakly against omicron have such a beneficial effect? After a series of test-tube and animal experiments, he’s put together a theory: It happens because our immune systems are quietly improving the quality of our vaccine or infection-induced protection over time.
The immune system keeps making and testing better and better antibodies, each generation of them more perfectly shaped to latch onto the viral proteins. The immune system doesn’t do this with conscious intelligence, but cells undergo a process akin to natural selection. A variety of similar antibodies are produced with each generation, saving only the “fittest” — those whose shapes work best to grab the virus’s essential proteins.
How long this process takes may vary some from person to person — Wesemann says it might be between four and six months. Then, once you get boosted, you’re boosting a much higher-quality set of antibodies.
Why that helps us fight omicron with a vaccine designed for a much older variant comes back to the way coronaviruses differ from influenza viruses. The flu can switch out whole components to foil immunity completely, but with Covid-19, at least so far, no variant has been able to change all the components of its spike protein.
There’s always something that’s “conserved,” as the scientists call it. So while the original vaccine can only attack part of omicron’s spike protein, a months-long period of refinement and a booster can do it with deadly precision — a small knife that cuts to the virus’s heart.
There are human genetic differences that make the boosters more effective in some people than others, and some severely immune compromised people won’t get the same protection from vaccines. But for most of us, there’s a big upside to getting a booster after your body has had time to refine its antibody library. So maybe an upside of the Biden administration’s embrace for the new boosters will be that it pulls in people who haven’t had any boosters and who stand to benefit from either version.
It’s possible that getting a second BA.5 booster six months later will give people even better protection but by then this variant may have disappeared. And what will replace it is unpredictable — as everything else has been in the nation’s two-and-a-half-year battle against Covid-19.
Bloomberg
