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

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

The findings, from laboratory-based experiments and published on March 4 in Physical Medicine, suggests that COVID-19 drugs and vaccines developed so far may become less effective as the new variant becomes dominant, as experts believe it will inevitably be. The researchers looked at variants from South Africa, the United Kingdom and Brazil.

“We are concerned that people we expect to have a protective level of antibodies because they have had COVID-19 or have been vaccinated against it may not be protected against the new variant,” said senior author Michael S. Diamond. MD, Ph.D., the professor of medicine of Herbert S. Gasser. “There is great variation in how much antibody a person produces in response to vaccination or natural infection. Some people produce very high levels, and they are likely to continue to be protected against the new, worrying variant. But some people, especially older and immune users, can not make such high levels of antibodies.If the level of the antibody needed for protection rises tenfold, as our data indicates, it may not be enough.The concern is that those who need the most protection, those who are least likely to have it. ‘

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

Consequently, spike has become the main target for COVID-19 medicine and vaccine developers. The three vaccines approved by the US Food and Drug Administration (FDA) for emergency use – made by Pfizer / BioNTech, Moderna and Johnson & Johnson – are both targeted. And powerful anti-spike antibodies have been selected for development in antibody-based drugs for COVID-19.

Viruses are always mutating, but the mutations that have emerged in SARS-CoV-2 have not threatened this strategy based on peaks for almost a year. This winter, rapidly spreading varieties were detected in the United Kingdom, South Africa, Brazil and elsewhere. It is of concern that the new variants all contain several mutations in their spike genes, which may reduce the efficacy of drugs targeted through peaks, which are now used to prevent or treat COVID-19. The most worrying new variants got 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 determine if the new variant antibodies made for the original form of the virus could evade, Diamond and colleagues, including first author Rita E. Chen, a graduate student in Diamond’s laboratory, tested 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 had been vaccinated with the Pfizer vaccine. They also tested antibodies in the blood of mice, hamsters and monkeys vaccinated with an experimental COVID-19 vaccine, developed at the Washington University School of Medicine, which can be given by nose. The B.1.1.7 (UK) variant can be neutralized with similar levels of antibodies as needed to neutralize the original virus. But the other two variants require 3.5 to 10 times as much antibody for neutralization.

Thereafter, they tested monoclonal antibodies: reproductions of individual antibodies mass-produced are exceptionally good at neutralizing the original virus. When the researchers tested the new viral variant against a panel of monoclonal antibodies, the results ranged from broadly effective to completely ineffective.

Since each virus variant contains multiple mutations in the spike gene, the researchers created a panel of viruses with single mutations so that they could analyze the effect of each mutation. Most variations in antibody efficiency can be attributed to a single change in the amino acid in the vein protein. This change, called E484K, was found in the B.1.135 (South Africa) and B.1.1.248 (Brazil) variants, but not B.1.1.7 (UK). The B.1.135 variant is widespread in South Africa, which may explain why one of the vaccinations tested in humans was less effective in South Africa than in the USA, where the variant is still rare, Diamond said. said.

“We do not 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 elements of the immune system may compensate for increased resistance to antibodies. This will be determined epidemiologically over time, as we will see what happens if these variants spread. Will we see? Re-infections? Will we see that vaccines are losing their effectiveness and drug resistance is emerging? I do not hope so. distribute and adapt treatment strategies. ”