When any virus enters the body, immune cells immediately churn out hordes of circulating antibodies. Foot soldiers of the immune system, these antibodies decay at variable rates depending on the vaccine or infection, after the duty is done. They may protect us for months or years but then dwindle in number, allowing possible reinfection. The 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 protection. Studies suggest that memory B cells for smallpox last at least 60 years after vaccination; those for Spanish flu, nearly a century. And 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 vigilant.
Until 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. Hope for a future without fear of COVID-19 comes down to circulating antibodies and memory B cells. Unlike 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 variants. Vaccination produces greater amounts of circulating antibodies than natural infection. But a new study suggests that not all memory B cells are created equal. While 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 by 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. Michel Nussenzweig Professor and Head, Laboratory of Molecular Immunology at Rockefeller University and his team resolved to tease out any differences in memory B cell evolution by comparing blood samples from convalescent COVID-19 patients to those from mRNA-vaccinated individuals who had never suffered a natural infection. Vaccination and natural infection elicited similar numbers of memory B cells, which rapidly evolved between the first and second dose of the Pfizer and Moderna vaccines, producing increasingly potent memory antibodies. But after two months, progress stalled. The memory B cells were present in large numbers and expressed potent antibodies, but the antibodies were not getting any stronger. Also, 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 infection. More 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 by natural infection might be expected to outperform those produced by mRNA vaccines, the researchers say. It is possible that the body responds differently to viruses that enter through the respiratory tract than those that are injected into our upper arms. Or perhaps an intact virus goads the immune system in a way that the lone spike protein represented by the vaccines simply cannot. Then again, maybe it’s that the virus persists in the naturally infected for weeks, giving the body more time to mount a robust response. The vaccine, on the other hand, is flushed out of the body mere days after triggering the desired immune response.
While according to the latest data the effectiveness of vaccines at protecting against symptomatic infection with variants of concern may be decreased, everything points to the conclusion that they remain somewhat effective in preventing severe forms of COVID-19, hospitalization and/or death. It is also known that cellular immune responses remain largely preserved. Nevertheless, at the moment, it is unclear whether variant-specific boosters will be necessary going forward. Such booster vaccines could either use the spike glycoprotein from the original SARS-CoV2 Wuhan strain or the one derived from a variant of concern. Data from Israel demonstrate that a third shot during the widespread circulation of delta variant can definitely provide short-term protection against confirmed infection and severe disease. However, it remains to be seen whether the spike protein will be able to mutate further to evade immune responses while at the same time preserving high levels of infectivity.
Along with the kinetics of immune responses, this will ultimately determine whether updated vaccines or boosters will be required and at what frequency.
- Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.
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