Vaccine-Induced Antibodies May Be Less Effective Against Several New Variants of SARS-CoV-2: Study

SARS-CoV-2, the virus responsible for COVID-19, mutated throughout the pandemic. New variants of the virus have appeared around the world, including variants that may have an increased ability to spread or escape the immune system. Such variants have been identified in California, Denmark, UK, South Africa and Brazil / Japan. Understanding the effectiveness of COVID-19 vaccines against these variants is essential 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, Alejandro Balazs, Ph.D., senior member of Ragon, found that neutralizing antibodies induced by Pfizer and Moderna COVID-19 vaccines were significantly less effective against variants first described in Brazil / Japan and South Africa. South. Balazs’ team used their experience measuring HIV neutralizing antibodies to create similar tests for COVID-19, comparing the effectiveness of antibodies against the original strain versus newer variants.

“We were able to harness the unique high-throughput capability already in place and apply it to SARS-CoV-2,” says Balazs, also an assistant professor of medicine at Harvard Medical School and an assistant researcher in the Department of Medicine at the MGH . “When we tested these new strains against vaccine-induced neutralizing antibodies, we found that the three new strains first described in South Africa were 20 to 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 than the original SARS-CoV-2 virus. “

Neutralizing antibodies, Balazs explains, work by binding tightly to the virus and preventing it from entering cells, thereby preventing infection. Like a key in a lock, this binding only occurs when the shape of the antibody and the shape of the virus are perfectly matched to each other. If the shape of the virus changes where the antibody attaches to it – in this case, in 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., resident physician in the MGH’s pathology department and first author of the study, “we found that mutations in a specific part of the protein spike called the receptor binding domains were more likely to help the virus resist neutralizing antibodies. “The three South African variants, which were the most resistant, all shared three mutations in the receptor binding domain. This may contribute to their 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, this does not mean that the vaccines will not be effective.

“The body has other methods of immune protection besides antibodies,” Balazs says. “Our findings don’t necessarily mean that vaccines won’t prevent COVID, only that the antibody part of the immune response may have trouble recognizing some of these newer 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 vaccine-derived immunity can help researchers develop next-generation vaccines that can provide protection against new variants. It can also help researchers develop more effective preventive methods, such as broadly protective vaccines that work against a wide variety of variants, regardless of which mutations develop.