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A team of US researchers has created an "atlas" that charts how 152 different antibodies attack a major piece of the SARS-CoV-2 machinery, the spike protein, as it has evolved since 2020. The study, published in the journal Cell, highlights antibodies that are able to neutralise the newer strains, while identifying regions of the spike protein that have become more resistant to attack.
"Emerging data show that vaccines still confer some protection from new SARS-CoV-2 variants, and our study shows how that works from an antibody standpoint," said Duane Wesemann, of the Division of Allergy and Clinical Immunology and Division of Genetics at Brigham and Women's Hospital.
"These data can help us think about what the best kind of booster vaccine might be by studying how the repertoire of human antibodies recognises the spike protein," Wesemann added.
The researchers examined the antibody-producing Memory B cells of 19 patients who were infected with SARS-CoV-2 in March of 2020, before the emergence of new variants.
They studied how these antibodies, as well as other antibodies that have been characterised by researchers, bind to spike protein models of the B.1.1.7 (Alpha), B.1351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2, which were first identified in the UK, South Africa, and Brazil, respectively.
An analysis of the Delta variant is currently underway.
Overall, the hundreds of antibodies they studied largely bind to seven major "footprints" on the spike protein.
While many of these antibodies "compete" to bind to the same regions of the early version of the SARS-CoV-2 spike protein, when it comes to newer strains, some of these antibodies lose their potency while others emerge as broadly responsive neutralisers, the researchers said.
In particular, antibodies binding to two of these spike protein regions, dubbed RBD-2 and NTD-1, were the most potent neutralisers of initial forms of the spike protein.
The B.1.351 spike variant proved to exhibit the greatest ability to evade existing antibody arsenals, escaping many RBD-2- and NTD-1-binding antibodies. Some antibodies binding another region, called S2-1, could recognise spike proteins from more distantly related viruses such as MERS, SARS, and common cold coronaviruses, the team explained.
"Now that we can identify the antibodies that are more broadly reactive to all of the variants, we can think about how to elicit them more strongly in a vaccine," Wesemann said.
