COVID-19: ‘Hybrid immunity’ may give us ‘edge’ over the coronavirus

In one of the most recent studies, scientists created a virus that contained 20 naturally occurring mutations of the spike protein of SARS-CoV-2, which is the protein that the virus uses to break into cells.

The spike proteins were resistant to antibodies belonging to unvaccinated people who had recovered from COVID-19 and to antibodies from people who had been vaccinated but never had COVID-19.

Remarkably, however, antibodies from individuals who had recovered from COVID-19 and were subsequently vaccinated neutralized these spike proteins.

These antibodies were also highly effective against six SARS-CoV-2 variants of concern, including Delta and Beta. In addition, they neutralized several viruses in the same family of coronaviruses, known as sarbecoviruses, that usually infect bats and pangolins.

Antibodies from these individuals also neutralized SARS-CoV-1, which is the coronavirus that caused the SARS outbreak 20 years ago.

The paper was originally available as a preprint, but it now appears in Nature.

One of the authors, the virologist Prof. Paul Bieniasz, has conducted several studies of hybrid immunity with his colleagues at Rockefeller University in New York.

He notes that hybrid immunity develops in people who had COVID-19 early in the pandemic and are then vaccinated 6–12 months later.

“While SARS-CoV-2 infection itself is thought to be quite short-lived, it is likely that some viral proteins and possibly even some infected cells persist, perhaps even for months,” he says.

He explains that this gives the immune system the chance to optimize and diversify its antibodies to recognize a wide range of variants. Vaccination then boosts the levels of these antibodies. He adds:

“One could reasonably predict that these individuals would 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.”

Another study, which appears in Science, found that in people who had recovered from COVID-19, a single dose of an mRNA vaccine boosted their levels of neutralizing antibodies against all variants of concern by up to 1,000-fold.

The authors conclude that their study highlights the importance of vaccinating people who have had COVID-19 in order to give them immunity to new variants.

In an accompanying comment article, the virologist Prof. Shane Crotty, Ph.D., from the La Jolla Institute for Immunology, CA, writes that a type of immune cell called a memory B cell is responsible for hybrid immunity.

These cells remember past encounters with a particular viral infection and generate the same antibodies when they encounter the same infection again.

However, they also create a range of mutated versions of this antibody, which Prof. Crotty calls “a stockpile of immunological variants.” These anticipate future infections with different versions of the same virus.

“These diverse memory B cells, created in response to the original infection, appear to be preemptive guesses by the immune system as to what viral variants may emerge in the future,” he writes.

People who have never had COVID-19 also benefit from this effect following vaccination, though to a lesser extent.

Another study that monitored the immunity of such individuals for 6 months after their second dose of an mRNA vaccine found that their antibody levels waned. However, their memory B cells recognized the Alpha, Beta, and Delta variants, and these cells increased in number 3–6 months after vaccination.

“The same antibody can actually detect, and presumably neutralize, the Alpha variant, the Beta variant, and, very likely, the Delta variant as well,” says senior author Prof. E. John Wherry, Ph.D., of the University of Pennsylvania Perelman School of Medicine, Philadelphia.

All the same, people who recover from COVID-19 and later have a first dose of a vaccine have stronger immunity than they would otherwise. This is because their immune system recognizes all 25 proteins that make up a SARS-CoV-2 virus.

In contrast, an mRNA vaccine only encodes a single protein — namely, the spike. Therefore, following vaccination, immune systems that have never encountered the virus itself only learn to recognize this protein and variants of it.

Prof. Wherry believes that in such cases, a booster dose of a vaccine will promote further evolution of these antibodies to provide stronger protection against variants.

The unpublished study, by researchers at the University of Pennsylvania Perelman School of Medicine in Philadelphia, is available on the preprint server BioRxiv.

“Based on all these findings, it looks like the immune system is eventually going to have the edge over this virus,” says Prof. Bieniasz.

“And if we’re lucky, SARS-CoV-2 will eventually fall into that category of viruses that gives us only a mild cold.”

What about related viruses that may jump from animals to humans to cause future pandemics, though? Can scientists develop a vaccine that protects against these as well as SARS-CoV-2?

The best approach may be to develop a vaccine that targets SARS and use it in conjunction with a SARS-CoV-2 vaccine.

Researchers led by the National University of Singapore reached this conclusion after finding that people in Singapore who recovered from SARS many years ago and recently received the Pfizer mRNA vaccine develop the strongest immunity against a broad range of sarbecoviruses.

Their antibodies neutralize not only SARS-CoV-2 variants of concern but also sarbecoviruses in bats and pangolins that have the potential to infect humans.

The study features in the New England Journal of Medicine.

“These findings show the feasibility of a pan-sarbecovirus vaccine strategy,” they write.

Their research suggests that a SARS vaccine may be a better candidate to protect against future sarbecovirus pandemics than a SARS-CoV-2 vaccine.

They found that people who had recovered from SARS and later received the Pfizer vaccine had better protection against sarbecoviruses than people who had recovered from COVID-19.

“This group of recovered COVID-19 patients vaccinated with mRNA certainly have high levels of antibodies against COVID based on published work and our own data,” co-author Prof. David Lye of the National Centre for Infectious Diseases in Singapore told Medical News Today.

“[B]ut they won’t be broadly neutralizing as demonstrated in our study against SARS and [viruses originating in] the rat and pangolin,” he added.

He told MNT that he and his colleagues are urging biotech companies to accelerate their development of SARS vaccines.

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