How antibodies work against the virus variants

Anyone who has recovered from an infection with the Sars-CoV-2 coronavirus has protective antibodies against the virus for a certain period of time. But to what extent do they also work against other virus variants? Researchers have now examined antibodies from people infected with the beta variant. The result: While some of the antibodies are specific for the beta variant, others offer broad immunity that can also protect to some extent against new strains such as Delta and Omicron. The results can also help in the further development of vaccination strategies.

In the course of the Covid-19 pandemic, numerous new variants of the virus have arisen as a result of mutations. Because the vaccines currently in use were developed against the wild type, they are less effective against some of the variants, leading to an increased incidence of breakthrough infections. This also applies to people who have recovered from an infection with Sars-CoV-2. It was previously unclear to what extent antibodies that form as a result of infection with a specific variant also protect against other variants.

Low activity against wild type

A team led by Momsen Reincke from the Charité Universitätsmedizin Berlin has now investigated this for the beta variant. “The beta variant of the coronavirus shows clear differences from the wild type, the original virus strain. Until the appearance of the now widespread omicron variant, it was the virus form that had developed furthest from the wild type, for which previous vaccines were designed,” says Reincke. “We now wanted to find out more about the exact antibody response to this variant – to see what conclusions can be drawn about the immune response in other variants. Since the corona virus will probably continue to mutate, we were interested in whether the antibodies found only work against the beta variant or whether they have broader potential.”

To do this, the researchers took blood samples from 40 convalescents from Germany and Austria who were infected with the beta variant. First, they tested the extent to which the antibodies in the blood serum were able to neutralize different strains of Sars-CoV-2. “The neutralizing activity against wild-type viruses was reduced about 20-fold compared to beta,” the researchers report. This result is relevant, among other things, because wild-type antigens have usually been used for tests that determine the antibody titer against the coronavirus. According to such tests, those who were infected with the beta variant probably have a low titer, since antibodies that are not directed against the wild type but are directed against other variants are insufficiently detected. “This adds complexity to the concept of setting a threshold for protective antibody titers,” the researchers write.

Beta antibodies against omicron

In the next step, the researchers examined the antibodies of those who had recovered in detail at the genetic level. “The immune response to the coronavirus produces a spectrum of antibodies that bind to different areas of the pathogen,” explains Reincke. Those that bind to the spike protein of the virus – the surface protein of Sars-CoV-2 that enables the virus to bind to and penetrate cells – are particularly effective. Reincke and his colleagues identified 81 antibodies in the blood samples that bind particularly strongly to the spike protein. In the beta variant, parts of the spike protein are modified by mutations. According to the analyzes, around half of the antibodies identified were specifically directed against the beta variant and were unable to do anything against other strains such as the wild type.

“Others, on the other hand, are very effective against the original virus strain and at the same time against some of the variants of concern, i.e. those virus forms that are considered to be of particularly high concern. Some of the antibodies against beta are even effective against the delta and omicron variants that are currently circulating,” says Reincke’s colleague Jakob Kreye. “The antibodies with broad activity are directed against areas of the spike protein that have largely remained the same in previous virus variants.” However, there are exceptions to this with Omicron: “We have found antibodies that work well against both beta and omicron and only weakly compared to other variants,” reports Kreye. “These special antibodies bind to sites on the spike protein that are quite similar in beta and omicron, but not in other variants.”

Cross-immunity against future variants?

According to the authors, the results may also be relevant for future vaccinations. “Even single antibodies against the wild type have broad activity. This is described in the literature and is also shown by studies from our laboratory,” says Reincke’s colleague Harald Prüß. “By combining these data and our current findings, we come to the conclusion that antibodies generated against different virus variants can complement each other and thus jointly improve the effectiveness of the immune response against newly emerging variants. Greatest possible diversity in the antibody response seems to make sense.”

It therefore makes sense to vaccinate against different known variants of the virus at the same time or one after the other. In this way, the probability of covering future variants through cross-immunity is increased. “This approach could be relevant for the further development of vaccination strategies, because it can be assumed that the pathogen will continue to change in the future,” says Kreye.

Source: Momsen Reincke (Charité Universitätsmedizin Berlin) et al., Science, doi: 10.1126/science.abm5835

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