Is a “natural” Covid-19 infection better than vaccination? It’s complicated

Hope for a future without fear of Covid-19 comes down to circulating antibodies and memory B cellsUnlike circulating antibodies, which peak soon after vaccination or infection only to fade a few months later, memory B cells can stick around to prevent severe disease for decades.

And they evolve over time, learning to produce successively more potent “memory antibodies” that are better at neutralizing the virus and more capable of adapting to variantsVaccination produces greater amounts of circulating antibodies than natural infectionBut a new study published in the journal Nature suggests that not all memory B cells are created equalWhile vaccination gives rise to memory B cells that evolve over a few weeks, natural infection births memory B cells that continue to evolve over several months, producing highly potent antibodies adept at eliminating even viral variants.

The findings highlight an advantage bestowed natural infection rather than vaccination, but the authors caution that the benefits of stronger memory B cells do not outweigh the risk of disability and death from Covid-19“While a natural infection may induce maturation of antibodies with broader activity than a vaccine does—a natural infection can also kill you,” says Michel CNussenzweig, the Zanvil ACohn and Ralph MSteinman professor and head of Rockefeller’s Laboratory of Molecular Immunology“A vaccine won’t do that and, in fact, protects against the risk of serious illness or death from infection.”

When any virus enters the body, immune cells immediately churn out hordes of circulating antibodiesFoot soldiers of the immune system, these antibodies burn bright but decay at variable rates depending on the vaccine or infection—they may protect us for months or years but then dwindle in number, allowing possible reinfectionThe immune system has a backup plan: an elite cadre of memory B cells that outlive circulating antibodies to produce so-called memory antibodies that provide long-term protectionStudies suggest that memory B cells for smallpox last at least 60 years after vaccination; those for Spanish flu, nearly a centuryAnd while memory B cells don’t necessarily block reinfection, they can prevent severe disease.

Recent studies have suggested that within five months of receiving a vaccine or recovering from a natural infection, some of us no longer retain sufficient circulating antibodies to keep the novel coronavirus at bay, but our memory B cells stand vigilantUntil now, however, scientists did not know whether the vaccines could be expected to provide the sort of robust memory B cell response seen after natural infection.

Nussenzweig and colleagues resolved to tease out any differences in memory B cell evolution comparing blood samples from convalescent Covid-19 patients to those from mRNA-vaccinated individuals who had never suffered natural infectionVaccination and natural infection elicited similar numbers of memory B cellsMemory B cells rapidly evolved between the first and second dose of the Pfizer and Moderna vaccines, producing increasingly potent memory antibodiesBut after two months, progress stalledThe memory B cells were present in large numbers and expressed potent antibodies, but the antibodies were not getting any strongerAlso, although some of these antibodies were able to neutralize Delta and other variants, there was no overall improvement in breadth.

With convalescent patients, on the other hand, memory B cells continued to evolve and improve up to one year after infectionMore potent and more broadly neutralizing memory antibodies were coming out with every memory B cell update.

There are several potential reasons that memory B cells produced natural infection might be expected to outperform those produced mRNA vaccines, the researchers sayIt is possible that the body responds differently to viruses that enter through the respiratory tract than those that are injected into our upper armsOr perhaps an intact virus goads the immune system in a way that the lone spike protein represented the vaccines simply cannotThen again, maybe it’s that the virus persists in the naturally infected for weeks, giving the body more time to mount a robust responseThe vaccine, on the other hand, is flushed out of the body mere days after triggering the desired immune response.

Regardless of the cause, the implications are clearWe can expect memory B cells to undergo limited volleys of evolution in response to mRNA vaccines, a finding that may have significant implications for the design and rollout of booster shotsA booster with the currently available mRNA vaccine would be expected to engage memory cells to produce circulating antibodies that are strongly protective against the original virus and somewhat less so against the variants, Nussenzweig says“When to administer the booster depends on the object of boosting,” he says“If the goal is to prevent infection, then boosting will need to be done after 6 to 18 months depending on the immune status of the individualIf the goal is to prevent serious disease boosting may not be necessary for years.”

Source: Rockefeller University

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