New evidence for COVID-19 antibodies, less effective vaccines against variants

New research at the University of Washington School of Medicine in St. Louis indicates that three new variants of the rapidly spreading virus that cause COVID-19 may escape the antibodies that act against the original form of the virus that generated the pandemic. With few exceptions, whether these antibodies are produced in response to vaccination or natural infection, or are purified antibodies intended for use as drugs, the researchers found that more antibodies are needed to neutralize the new variants.

The results, from laboratory-based experiments and published on March 4 in Nature Medicine, suggest that the COVID-19 drugs and vaccines developed so far may become less effective as the new variants become dominant, as experts say will inevitably happen. The researchers analyzed variants from South Africa, the United Kingdom and Brazil.

“We are concerned that people who expected to have a level of protection from antibodies because they had COVID-19 or were vaccinated against it, may not be protected against the new variants,” said senior author Michael S. Diamond, MD, Ph.D ., Professor of Medicine Herbert S. Gasser. “There is a wide variation in the amount of antibodies that a person produces in response to vaccination or natural infection. Some people produce very high levels and would probably still be protected against new and worrying variants. But some people, especially the elderly and immunocompromised, may not produce such high levels of antibodies. If the level of antibodies needed for protection goes up tenfold, as our data indicates, they may not have enough. The concern is that the people who need protection most are the least likely to have it . “

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

Consequently, the peak has become the main target for COVID-19 drug and vaccine developers. The three vaccines authorized by the Food and Drug Administration (FDA) for emergency use in the United States – made by Pfizer / BioNTech, Moderna and Johnson & Johnson – target the peak. And potent anti-pico antibodies have been selected for development in drugs based on antibodies to COVID-19.

Viruses are always mutating, but for almost a year the mutations that emerged in SARS-CoV-2 did not threaten this spike-based strategy. So, this winter, fast-spreading variants were detected in the UK, South Africa, Brazil and elsewhere. Stimulating concern, all new variants carry multiple mutations in their peak genes, which could decrease the effectiveness of peak-targeted drugs and vaccines that are now being used to prevent or treat COVID-19. The most worrying new variants were named B.1.1.7 (from the United Kingdom), B.1.135 (South Africa) and B.1.1.248, also known as P.1 (Brazil).

To assess whether the new variants could escape antibodies made to the original form of the virus, Diamond and colleagues, including first author Rita E. Chen, a graduate student in Diamond’s laboratory, tested the antibodies’ ability to neutralize three variants of the virus in the laboratory.

The researchers tested the variants against antibodies in the blood of people who recovered from SARS-CoV-2 infection or were vaccinated with the Pfizer vaccine. They also tested antibodies in the blood of mice, hamsters and monkeys that were vaccinated with an experimental vaccine COVID-19, developed at the University of Washington School of Medicine, which can be administered through the nose. Variant B.1.1.7 (UK) can be neutralized with levels of antibodies similar to those needed to neutralize the original virus. But the other two variants required 3.5 to 10 times more antibodies for neutralization.

Then they tested monoclonal antibodies: mass-produced replicas of individual antibodies that are exceptionally good at neutralizing the original virus. When the researchers tested the new viral variants against a panel of monoclonal antibodies, the results ranged from largely effective to completely ineffective.

As each variant of the virus carried multiple mutations in the spike gene, the researchers created a panel of viruses with unique mutations so that they could analyze the effect of each mutation. Most of the variation in antibody effectiveness can be attributed to a single amino acid change in the peak protein. This change, called E484K, was found in variants B.1.135 (South Africa) and B.1.1.248 (Brazil), but not B.1.1.7 (United Kingdom). Variant B.1.135 is common in South Africa, which may explain why one of the vaccines tested on people was less effective in South Africa than in the United States, where the variant is still rare, Diamond said.

“We don’t know exactly what the consequences of these new variants will be,” said Diamond, also a professor of molecular microbiology and pathology and immunology. “Antibodies are not the only protective measure; other elements of the immune system can compensate for increased resistance to antibodies. This will be determined over time, epidemiologically, as we will see what happens as these variants spread. We will see reinfections. “Will we see vaccines lose effectiveness and drug resistance emerge? I hope not. But it is clear that we will need to continually track antibodies to ensure they are still working as new variants appear and spread and potentially adjust our vaccine and antibody strategies. of treatment. ”