Killing antibodies actuated by COVID-19 vaccines less successful against new variants

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• Source: Massachusetts General Hospital


• Date: 15 Mar,2021

SARS-CoV-2, the virus that causes COVID-19, has mutated through the pandemic. New variants of this virus have arisen around the world, including variants that might possess increased capacity to spread or evade the immune system. Such variations have been identified in California, Denmark, the U.K., South Africa and Brazil/Japan. Recognizing how well the COVID-19 vaccines work against these variations is vital in the efforts to halt the global pandemic, and is the subject of new study 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, PhD, discovered that the neutralizing antibodies induced by the Pfizer and Moderna COVID-19 vaccines were significantly less effective against the variations first described in Brazil/Japan and South Africa. Balazs’s team used their experience measuring HIV neutralizing antibodies to create similar assays for COVID-19, comparing how well the antibodies worked against the original strain versus the new versions.\

We were able to leverage the unique high-throughput capacity that was already in place and apply it to SARS-CoV-2. When we tested these new strains against vaccine-induced neutralizing antibodies, we found that the three new strains first described in South Africa were 20-40 times more resistant to neutralization, and the two strains first described in Brazil and Japan were five to seven times more resistant, compared to the original SARS-CoV-2 virus.”

Alejandro Balazs, Assistant Professor of Medicine, Harvard Medical School and Assistant Investigator, Department of Medicine, MGH

Like a key in a lock, this binding only happens when the antibody’s shape and the virus’s contour are perfectly matched to each other. If the form of the virus changes where the antibody attaches to it – in this case, in SARS-CoV-2’s spike protein – then the antibody may no longer be able to recognize and neutralize the virus also. The virus could then be described as resistant to neutralization.

“In particular,” says Wilfredo Garcia-Beltran, MD, PhD, a resident doctor in the Department of Pathology at MGH and first author of the study,”we found that mutations in a certain part of the spike protein known as the receptor binding domain were more likely to help the virus resist the neutralizing antibodies.” This may contribute to their high resistance to neutralizing antibodies.

Currently, all approved COVID-19 vaccines work by instructing the body to produce an immune response, including antibodies, against the SARS-CoV-2 spike protein. While the ability of these variants to withstand neutralizing antibodies is about, it does not mean the vaccines won’t succeed.

“The body has other procedures of immune protection besides antibodies,” says Balazs. “Our findings do not necessarily mean that vaccines won’t prevent COVID, only that the antibody portion of the immune response might have trouble recognizing some of the new versions.”

Like all viruses, SARS-CoV-2 is forecast 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 could provide protection against new versions. It can also help researchers develop more effective preventative methods, like broadly protective vaccines that work against a huge array of variants, regardless of which mutations develop.