A hospital worker and COVID patient in South Africa, where a new variant of SARS-CoV-2 has been identified.Credit: Rodger Bosch / AFP / Getty
As concerns about faster-spreading variants of coronavirus grow, laboratories worldwide are exploring the biology of these viruses. Scientists want to understand why SARS-CoV-2 variants identified in the UK and South Africa appear to spread so rapidly and whether they can reduce the potency of vaccines or overcome natural immunity and lead to reinfections.
“Many of us are scrambling to make sense of the new variant, and the million-dollar question is what significance it will have for the effectiveness of vaccines currently being administered,” said Jeremy Luban, a virologist at the University of Massachusetts. School in Worcester.
The first laboratory results are penetrated and much more is expected in the coming days, as researchers want to investigate the virus variants and their constituent mutations in cell and animal models of SARS-CoV-2, and this against antibodies caused by vaccines and natural remedies. word, test. infections. “By next week, we have a lot more information,” said Vineet Menachery, a virologist at the University of Texas Medical Branch in Galveston, whose team is ready to study the variants.
Underlying biology
Researchers noticed both coronavirus variants in late November and early December 2020 by genome sequencing. A COVID-19 genomics trial in the UK has determined that a virus variant now known as B.1.1.7 was behind the rising case numbers in the south east of England and London; the variant has now spread to the rest of the UK and has been detected in dozens of countries worldwide (see ‘Viral Series’).
And a team led by bio-informatics Tulio de Oliveira at the University of KwaZulu-Natal in Durban, South Africa, joins1 a rapidly growing epidemic in the country’s Eastern Cape province after a coronavirus variant they call 501Y.V2. The British and South African variants have emerged independently, but both have a large number of mutations – some of which are similar – in the coronavirus protein, through which the virus identifies and infects host cells, and which serves as our primary target. immune response.
Source: Data from GISAID / Angie Hinrichs, University of California, Santa Cruz, Genomics Institute; data from 6 January 2021.
Epidemiologists studying the growth of the B.1.1.7 variant in the United Kingdom estimate that it is approximately 50% more transmissible than existing viruses in circulation.2 an insight that contributed to the British government’s decision to enter a third national exclusion on 5 January. “The epidemiology has really shown us the way here,” said Wendy Barclay, a virologist at Imperial College London and a member of a group advising the British government on its response to B.1.1.7.
But it is important, Barclay adds, that scientists determine the underlying biology. “If we understand what characteristics of the virus make it more communicable, we can be more informed about policy decisions.”
One challenge is to unravel the effects of the mutations that distinguish the British and South African lineage from their relatives. The B.1.1.7 variant contains 8 changes that affect the ear protein, and a few other genes; samples of the South African 501Y.V2 variant have up to 9 changes to the vein protein. Working out what is responsible for the rapid spread of the variants and other properties is a ‘huge challenge’, says Luban. “I do not think there is a single mutation that justifies it all.”
Most of the focus is on a change in the protein shared by both sexes called N501Y. This mutation changes a portion of the peak, called the receptor binding domain, that locks onto a human protein to allow infection. One hypothesis indicated in previous studies is that the N501Y change can attach the virus more strongly to cells, facilitating infection, Barclay says.
The N501Y mutation is one of several that Menachery’s team is preparing to test hamsters, a model for SARS-CoV-2 transmission. He was part of a team that reported3 last year that a mutation other than the peak protein enables viruses to grow to greater levels in the upper airways of hamsters, compared to viruses that do not change. “This is what I expect with these mutations,” he says. “If that’s the case, it’s going to improve its portability.” A report published in late December supports the hypothesis: it found more SARS-CoV-2 genetic material in the swabs of people infected with the B.1.1.7 variant, compared to those infected with viruses without the N501Y change.
Antibody tests
The rapid spread of the variants has led to efforts to limit their distribution through closures, boundary restrictions and increased surveillance. The feeling of urgency contributes to the concern that the variant immune responses caused by vaccines and previous infection may weaken. Both variants contain mutations in regions of the ear protein that are recognized by powerful virus-blocking ‘neutralizing’ antibodies: the receptor-binding domain and a portion called the N-terminal domain, says Jason McLellan, a structural biologist at the University of Texas . Austin, who is studying coronavirus ear proteins. This increases the possibility that antibodies against these regions may be affected by the mutations.
As a result, academic and government researchers and vaccine developers are now working 24 hours a day to address the demand. “It’s a crazy speed,” says Pei-Yong Shi, a virologist at UTMB who is working with Pfizer to analyze blood from participants in their successful vaccination study. In a related experiment, a team led by his colleague Menachery found that the 501Y mutation at least did not drastically affect the activity of neutralizing antibodies in restorative serum – the antibody-containing portion of blood taken from people recovering has COVID infection. . This suggests that the 501Y mutation is unlikely to alter immunity, adds Menachery, who posted the data. Twitter on December 22nd.
But other mutations can. There is another receptor-binding domain mutation that Oliveira’s team identified in the 501Y.V2 variant called E484K. His team is working with virologist Alex Sigal at the Africa Health Research Institute in Durban to test the variant against restorative serum and serum from people vaccinated in trials. The first results of these studies should be made public within a few days, says de Oliveira.
Immune escape
There is emerging evidence that the E484K mutation enables the virus to escape the immune responses of some people. In a preview of December 284, a team led by immunologist Rino Rappuoli, at the Fondazione Toscana Life Sciences in Siena, Italy, cultivated SARS-CoV-2 in the presence of low levels of one person’s recovery problem. The aim was to select viral mutations that evoke the diverse repertoire of antibodies generated in response to infection. “The experiment did not necessarily have to work,” says McLellan, a co-author. But within 90 days, the virus picked up three mutations that made it impermeable to the person’s serum – including the E484K mutation in the South African variant and N-terminal domain changes found in it and the British variant. “It was surprising,” says McLellan, because it suggested that the individual’s entire antibody response to SARS-CoV-2 was directed to a small portion of the ear protein.
The laboratory-developed strain was less resistant to restorative sera from other humans. But the experiment suggests that mutations such as E484K and N-terminal domain are altered by both variants can affect how antibodies generated by vaccines and previous infection recognize it, McLellan says.
Both Moderna and BioNtech, which developed an RNA vaccine with drug giant Pfizer, said they expected their push against the British variant to work and that tests were underway. These studies involve measuring the activity of neutralizing antibodies in the blood of people who have received the vaccine.
An urgent question is whether such changes will alter the true effectiveness of vaccines, says Jesse Bloom, a viral evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington. In a pre-print of 4 January5, his team also reported that E484K and several other mutations can escape recognition by antibodies in people’s recovery problem to varying degrees.
But Bloom and other scientists are hopeful that the mutations in the variants will not significantly impair the action of vaccines. The shots tend to elicit tremendous levels of neutralizing antibodies, so a small drop in their strength over the variants may not matter. Other arms of the immune response caused by vaccines, such as T cells, may not be affected. “If I had to bet now, I would say that the vaccines will remain effective for the things that really matter – to keep people from becoming terminally ill,” says Luban.