Escape immune response

Source: By The Indian Express

Fast-spreading variants of the SARS-CoV-2 coronavirus carry mutations that enable the virus to escape some of the immune response created naturally or by vaccination. A new study from scientists at Scripps Research, along with collaborators in Germany and the Netherlands, has found key details of how these escape mutations work.

The scientists, whose study appears in Science, used structural biology techniques to map at high resolution how important classes of neutralising antibodies bind to the original pandemic strain of SARS-CoV-2—and how the process is disrupted by mutations found in new variants first detected in Brazil (P.1), the United Kingdom (B.1.1.7), South Africa (B.135.1) and India (B.1.617).

A release published on the Scripps Research website says the research highlights that several of these mutations are clustered in one site, known as the “receptor binding site”, on the spike protein of the virus. Other sites on the receptor binding domain are unaffected.

Because of the newer variants’ potential to spread and cause disease—perhaps in some cases, despite vaccination—scientists consider it urgent to discover how the variants manage to escape much of the prior immune response in the body, including the antibody response.

In the study, the researchers focused mainly on three mutations in the SARS-CoV-2 spike protein: K417N, E484K and N501Y. Alone or in combination, these mutations are found in most major SARS-CoV-2 variants. All of the mutations are found in the SARS-CoV-2 receptor binding site, which is where the virus attaches to host cells.

The researchers tested representative antibodies from the major classes that target the general area in and around the receptor binding site. They found that many of these antibodies lose their ability to effectively bind and neutralise the virus when the mutations are present.

Using structural imaging techniques, the team then mapped the relevant portion of the virus at atomic-scale resolution to examine how the mutations affect sites where antibodies otherwise would bind and neutralise the virus.

The findings suggest that while antibody responses to the SARS-CoV-2 receptor binding site can be very potent in neutralizing the original Wuhan strain, certain variants are able to escape—perhaps eventually necessitating updated vaccines.

At the same time, the study underlines the fact that the three key viral mutations, which SARS-CoV-2 seems inherently prone to develop, do not alter other vulnerable sites on the virus outside the receptor binding site. The researchers specifically showed that virus-neutralising antibodies targeting two other areas outside the receptor binding site were largely unaffected by these three mutations.

This suggests that future vaccines and antibody-based treatments could provide broader protection against SARS-CoV-2 and its variants by eliciting or utilising antibodies against parts of the virus that lie outside the receptor binding site. The researchers note that broad protection against variants may be necessary if, as seems likely, the virus becomes endemic in the population.