ANTIBODIES, VACCINES LESS EFFECTIVE AGAINST CORONAVIRUS VARIANTS: STUDY

Fri 05 March 2021:

COVID-19 antibody-based drugs and vaccines developed so far may become less effective as new variants of the novel coronavirus spread widely, according to a new study.

The research, published in the journal Nature Medicine, noted that the three fast-spreading variants of the coronavirus first reported in South Africa, the UK and Brazil, can evade antibodies that work against the original form of the virus that sparked the pandemic.

According to the scientists, including those from the Washington University School of Medicine in St. Louis in the US, more of antibodies produced in response to vaccination or natural infection, or purified antibodies intended for use as drugs, is needed to neutralise these novel coronavirus varieties, compared to the levels needed to counter the original virus lineage from Wuhan, China.

“We’re concerned that people whom we’d expect to have a protective level of antibodies because they have had COVID-19 or been vaccinated against it, might not be protected against the new variants,” said study senior author Michael S. Diamond from the Washington University School of Medicine in St. Louis.

The researchers said there is wide variation in how much antibody a person produces in response to vaccination or natural infection.

“Some people produce very high levels, and they would still likely be protected against the new, worrisome variants. But some people, especially older and immunocompromised people, may not make such high levels of antibodies,” Diamond said.

“If the level of antibody needed for protection goes up tenfold, as our data indicate it does, they may not have enough. The concern is that the people who need protection the most are the ones least likely to have it,” he added.

According to the researchers, people infected with the coronavirus generate the most protective antibodies against the virus spike protein which enables it to enter host cells.

Over the course of the pandemic, the scientists said neutralising the spike protein became an widely used strategy for developing antibody-based drugs against the coronavirus as well as in vaccine development.

While for nearly a year the mutations that arose in the virus did not threaten this spike-based strategy, the scientists said fast-spreading variants detected in the UK, South Africa, Brazil and elsewhere carried multiple alterations in their spike genes that could lessen the effectiveness of spike-targeted drugs and vaccines.

They said the most worrisome new variants were B.1.1.7 from the UK, B.1.135 from South Africa, and B.1.1.248, also known as P.1, first reported in Brazil.

In the current research, the scientists tested the ability of antibodies to neutralise three virus variants in the laboratory.

They tested the variants against antibodies in the blood of people who had recovered from the coronavirus infection or were vaccinated with the Pfizer COVID-19 vaccine.

The researchers also tested 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, that can be given through the nose.

According to the study, the B.1.1.7 variant could be neutralised with similar levels of antibodies as were needed to neutralise the original virus, but the other two variants required from 3.5 to 10 times as much antibody for neutralization.

When the researchers tested the new viral variants against a panel of mass-produced replicas of individual antibodies called monoclonal antibodies, the results ranged from broadly effective to completely ineffective.

They said most of the variation in antibody effectiveness could be attributed to a change in a single amino acid building block that makes up the spike protein.

This change, called E484K, was found in the South African and Brazilian variants, but not in the one from UK, the study noted.

“We don’t exactly know what the consequences of these new variants are going to be yet,” said Diamond.

“Antibodies are not the only measure of protection; other elements of the immune system may be able to compensate for increased resistance to antibodies. That’s going to be determined over time, epidemiologically, as we see what happens as these variants spread,” he added.

The scientists call for continuous testing of the ability of antibodies to work against new variants to potentially adjust vaccines and antibody-treatment strategies.