September 9, 2021

'Hybrid' coronavirus exposure may drive powerful—almost 'superhuman'—immunity

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    Several studies suggest that some vaccinated individuals who were also previously infected have a "superhuman" immunity to Covid-19—which not only protects them against current coronavirus variants, but may also combat future ones, Michaeleen Doucleff writes for NPR's "Goats and Soda."

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    Studies find evidence of 'superhuman' immunity to Covid-19

    According to Doucleff, a series of studies have found that some people have "superhuman" or "hybrid" immunity against Covid-19, which offers them more robust protection against different coronavirus variants.

    Individuals who produce this powerful immune response have had hybrid exposure to the coronavirus through natural infection and subsequent vaccination, Doucleff reports, enabling the body to produce not only very high antibody levels, but also very flexible antibodies—antibodies that appear capable of fending off current and future variants.

    For instance, in one pre-print study published in bioRxiv, researchers found that antibodies in these highly protected individuals were able to neutralize six coronavirus variants of concern tested, including delta and beta. The antibodies were also able to neutralize other viruses related to SARS-CoV-2, including one from bats, two from pangolins, and SARS-CoV-1, the virus that caused the first coronavirus pandemic.

    In fact, in separate research, Theodora Hatziioannou, a virologist at Rockefeller University who has helped lead several studies on hybrid immunity, and her colleagues found that antibodies from these individuals were even able to combat a virus specifically designed to resist neutralization. The engineered virus had 20 mutations that were known to prevent SARS-CoV-2 antibodies from binding to it. While antibodies from people who had only received vaccines or only had prior infection were "essentially useless" against the virus, the antibodies from people with hybrid immunity were able to neutralize it, Doucleff writes.

    "One could reasonably predict that these people will be quite well protected against most—and perhaps all of—the SARS-CoV-2 variants that we are likely to see in the foreseeable future," Paul Bieniasz, a virologist at Rockefeller University who helped lead the study and several others like it, said.

    According to Hatziioannou, these findings show how powerful mRNA vaccines can be in people who have been previously infected with the coronavirus. "After natural infections, the antibodies seem to evolve and become not only more potent but also broader," she said. "They become more resistant to mutations within the (virus)."

    How common is this type of immunity?

    While researchers are still not sure if everyone who has had Covid-19 and then subsequently been vaccinated with mRNA vaccines will have similar immune responses, Hatziioannou believes it is quite common.

    "With every single one of the [14] patients we studied, we saw the same thing," she said. "Those people have amazing responses to the vaccine… I think they are in the best position to fight the virus."

    According to Doucleff, several other studies support Hatziioannou's hypothesis that hybrid exposure to the coronavirus will lead to a more powerful immune response. For example, one study published in the New England Journal of Medicine found that people who had been infected with SARS-CoV-1 in 2002 or 2003 and then received an mRNA vaccine also produced high levels of neutralizing antibodies that were effective against coronavirus variants and other similar viruses.

    Could a third vaccine dose also lead to 'hybrid immunity'?

    According to Hatziiannou, it is unclear whether other exposures to the coronavirus—either through a breakthrough infection or an additional vaccine dose for those who had not been previously infected—would produce a similarly robust immune response.

    "I'm pretty certain that a third shot will help a person's antibodies evolve even further, and perhaps they will acquire some breadth [or flexibility]," she said, "but whether they will ever manage to get the breadth that you see following natural infection, that's unclear."

    However, John Wherry, an immunologist at the University of Pennsylvania, suggests that it could be possible. "In our research, we already see some of this antibody evolution happening in people who are just vaccinated," he said, "although it probably happens faster in people who have been infected."

    In a preprint study in bioRxiv, Wherry and his colleagues found that over time, people with two vaccine doses and no prior infection began to produce more flexible antibodies, which can better identify different coronavirus variants of concern.

    According to Wherry, these findings suggest that a third vaccine dose would likely boost antibodies even more and push them to evolve further—meaning that a person would be better protected against any new variants that may emerge.

    "Based on all these findings, it looks like the immune system is eventually going to have the edge over this virus," Bieniasz said. "And if we're lucky, SARS-CoV-2 will eventually fall into that category of viruses that gives us only a mild cold." (Doucleff, "Goats and Soda," NPR, 9/7)

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