New variants of COVID-19 can avoid antibodies that work against the original form of the virus

New research at Washington University School of Medicine in St. Louis. Louis reveals that three new, rapid modifications of the virus that causes COVID-19 can avoid antibodies that work against the original form of the virus that triggered the pandemic.

With very few exceptions, whether such antibodies were released in response to a vaccine or a natural infection, or whether purified antibodies were intended for use as drugs, the researchers found it necessary. more antibody to neutralize the new variables.

The findings, from laboratory-based experiments and published March 4 in Natural Medicine, suggest that COVID-19 drugs and vaccines developed to date may be as effective as the new variables. gaining the upper hand, as experts say will be inevitable. The researchers looked at changes from South Africa, the United Kingdom and Brazil.

We are concerned that people who would expect a protective level of antibodies because they have received COVID-19 or been vaccinated against it may not be protected from the new variants. “

Michael S. Diamond, MD, PhD, Senior Research Fellow, Herbert S. Gasser Professor of Medicine

“There is a wide variation in the level of antibody a person makes in response to a vaccine or a natural infection. Some people produce very high levels, and would be more likely to be immune. from the worrying new variables.

But some people, especially the elderly and people with vaccinations, may not make such high levels of antibodies. If the level of antibody needed for protection goes up tenfold, as our data shows, they may not have enough. The concern is that the people most in need of protection are the most likely to have it. “

The virus that causes COVID-19, called SARS-CoV-2, uses a protein called a spike to enter and enter cells. People with SARS-CoV-2 infection generate the most protective antibodies against the spike protein.

As a result, spike became a major target for COVID-19 drug and vaccine developers. The three vaccines authorized by the Food and Drug Administration (FDA) for emergency use in the US -; produced by Pfizer / BioNTech, Moderna and Johnson & Johnson -; both target spike. And strong antibodies against spike were selected for their development to antibody-based drugs for COVID-19.

Viruses are always suppressed, but for nearly a year the mutations that occurred in SARS-CoV-2 did not threaten this spike-based strategy. Then, this winter, rapid changes were found in the United Kingdom, South Africa, Brazil and elsewhere.

Concerned, all the new variants carry a number of mutations in their spike genes, which may reduce the effectiveness of drugs and vaccines that target spike are now used to prevent or treat COVID-19 . The most worrying new changes got the names B.1.1.7 (from the UK), B.1.135 (South Africa) and B.1.1.248, also known as P.1 (Brazil).

To find out if the new variants could avoid antibodies made for the original form of the virus, Diamond and colleagues, including first author Rita E. Chen, a graduate student, did so. in a Diamond laboratory, a test of the ability of antibodies to neutralize three virus variants in the laboratory. .

The researchers tested the variants against antibodies in the blood of people who had recovered from SARS-CoV-2 infection or received the Pfizer vaccine. They also tested antibodies in the blood of mice, hamsters and monkeys that received the COVID-19 experimental vaccine, developed at the University of Washington School of Medicine, which can be given through the nose.

The B.1.1.7 (RA) variant could be neutralized by levels of antibodies as needed to neutralize the original virus. But the other two variables required from 3.5 to 10 times as much refraction for neutralization.

They then tested monoclonal antibodies: a mass-produced replica of individual antibodies that are excellent at neutralizing the original virus. When the researchers tested the new viral variants against a panel of monoclonal antibodies, the results ranged from generally effective to completely ineffective.

Because there were several mutations in the spike gene in each virus variant, the researchers created a panel of viruses with single mutations to find out the effect of each mutation. Most of the difference in antibody efficiency could be attributed to a single amino acid change in the spike protein.

This change, called E484K, was found in variables B.1.135 (South Africa) and B.1.1.248 (Brazil), but not B.1.1.7 (UK). The variant B.1.135 is widespread in South Africa, which may explain why one of the vaccines tested in humans was less effective in South Africa than in the US, where the variant still rare, Diamond said.

“We don’t know for sure what the impact of these new variables will be yet,” said Diamond, who is also a professor of molecular microbiology and pathology & immunology. “Antibodies are not the only measure of immunity; other elements of the immune system may be able to compensate for increased resistance to antibodies.

That’s going to be proven over time, epidemiologically, because we’ll see what happens as these variables spread. Will we see feedback? Will we see vaccines lose effectiveness and drug resistance emerge? I hope not. But it is clear that we need to screen antibodies regularly to make sure they are still working as new changes arise and spread and that our vaccines and antibody treatment strategies may change. “