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

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

The results, derived from laboratory 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 they inevitably will. The researchers studied variants from South Africa, the United Kingdom and Brazil.

“We are concerned that people who we would expect to have a protective level of antibodies to because they have had COVID-19 or have been vaccinated against it, may not be protected against the new variants,” said the senior author Michael S. Diamond, MD, Ph.D., Herbert S. Gasser professor of medicine. “The amount of antibody produced by a person in response to vaccination or natural infection varies widely. Some people produce very high levels and would still be protected against the new worrisome 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 increases tenfold, as our data indicates, they may not get enough. The problem is that people who have it. the more in need of protection are the least likely to have it. “

The virus that causes COVID-19, known as SARS-CoV-2, uses a protein called a peak to attach itself and get inside cells. People infected with SARS-CoV-2 generate the most protective antibodies against the spike protein.

As a result, the peak has become the primary target for developers of COVID-19 drugs and vaccines. The three vaccines cleared by the Food and Drug Administration (FDA) for emergency use in the United States – manufactured by Pfizer / BioNTech, Moderna and Johnson & Johnson – are both targeting a peak. And strong anti-spike antibodies have been selected for development into antibody drugs for COVID-19.

Viruses are still mutating, but for almost a year the mutations that appeared in SARS-CoV-2 did not threaten this peak-based strategy. Then this winter, rapidly spreading variants were detected in the UK, South Africa, Brazil and elsewhere. Of concern, the new variants all carry multiple mutations in their spike genes, which could decrease the effectiveness of spike-targeted drugs and vaccines currently used to prevent or treat COVID-19. The most disturbing new variants were given the names of B.1.1.7 (from the UK), 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 for the original form of the virus, Diamond and her colleagues, including first author Rita E. Chen, a graduate student of Diamond’s lab, tested the ability of the antibodies to neutralize three variants. virus in the laboratory. .

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

Next, they tested monoclonal antibodies: mass-produced replicas of individual antibodies that are exceptionally effective 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.

Since each virus variant 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 efficacy could be attributed to a single amino acid change in the spike protein. This change, called E484K, was found in variants B.1.135 (South Africa) and B.1.1.248 (Brazil), but not in B.1.1.7 (UK). The B.1.135 variant is prevalent in South Africa, which may explain why one of the vaccines tested in humans was less effective in South Africa than in the United States, where the variant is still rare, said Diamond.

“We don’t yet 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 measure of protection; other parts of the immune system may be able to compensate for increased resistance to antibodies. This will be determined over time, epidemiologically, as we will see what happens as we go. and as these variants spread. Will we see vaccines lose their effectiveness and drug resistance emerge? I hope not. But it is clear that we will have to continually screen for antibodies to make sure they still work as new variants appear and spread and potentially adjust our vaccine and antibodies. treatment strategies. ”