Vaccine-induced antibodies may be less effective against several new variants of SARS-CoV-2: study

SARS-CoV-2, the virus that causes COVID-19, mutated during the pandemic. New variants of the virus have emerged around the world, including variants that may have a greater ability to spread or escape the immune system. These variants have been identified in California, Denmark, the United Kingdom, South Africa and Brazil / Japan. Understanding how the COVID-19 vaccines work against these variants is vital in efforts to stop the global pandemic and is the subject of new research from the Ragon Institute of MGH, MIT and Harvard and Massachusetts General Hospital.

In a study recently published in Cell, Ragon Core Member Alejandro Balazs, Ph.D., found that the neutralizing antibodies induced by the Pfizer and Moderna COVID-19 vaccines were significantly less effective against the variants first described in Brazil / Japan and South Africa. The Balazs team used his experience measuring HIV neutralizing antibodies to create similar assays for COVID-19, comparing how well the antibodies worked against the original strain and the new variants.

“We were able to leverage the unique high-throughput capacity that already existed and apply it to SARS-CoV-2,” said Balazs, who is also an assistant professor of medicine at Harvard Medical School and an assistant researcher in the Department of Medicine at MGH. “When we tested these new strains against vaccine-induced neutralizing antibodies, we found that the three new strains described for the first time in South Africa were 20-40 times more resistant to neutralization, and the two strains described for the first time in Brazil and Japan were five to seven times more resistant, compared to the original SARS-CoV-2 virus. “

Neutralizing antibodies, explains Balazs, act by binding strongly to the virus and blocking it from entering cells, thus preventing infection. Like a key in a lock, this connection only happens when the shape of the antibody and that of the virus match each other perfectly. If the shape of the virus changes where the antibody binds to it – in this case, the SARS-CoV-2 spike protein – then the antibody may no longer be able to recognize and neutralize the virus as well. The virus would then be described as resistant to neutralization.

“In particular,” says Wilfredo Garcia-Beltran, MD, Ph.D., a resident physician in the Department of Pathology at MGH and the study’s first author, “we found that mutations in a specific part of the spike protein called the domain of binding to the receptor was more likely to help the virus resist neutralizing antibodies. “The three South African variants, which were the most resistant, shared three mutations in the receptor-binding domain. This can contribute to its high resistance to neutralizing antibodies.

Currently, all approved COVID-19 vaccines work by teaching the body to produce an immune response, including antibodies, against the SARS-CoV-2 spike protein. While the ability of these variants to resist neutralizing antibodies is of concern, that does not mean that vaccines will not be effective.

“The body has other methods of immunological protection in addition to antibodies,” says Balazs. “Our findings do not necessarily mean that vaccines will not prevent COVID, just that the antibody portion of the immune response may have trouble recognizing some of these new variants.”

Like all viruses, SARS-CoV-2 is expected to continue to mutate as it spreads. Understanding which mutations are most likely to allow the virus to evade immunity derived from the vaccine can help researchers develop next-generation vaccines that can provide protection against new variants. It can also help researchers to develop more effective preventive methods, such as broad protection vaccines that act against a wide variety of variants, regardless of which mutations develop.

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