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Neutralising antibodies may be less effective against SA variant — French study

Antibodies from people convalescing from or vaccinated against COVID-19 can neutralise the B.1.1.7 SARS-CoV-2 variant (first identified in the UK), but they may be either unable or less able to neutralise the B.1.351 variant (first identified in South Africa) when compared to the reference strain D614G. The study findings based on laboratory experiments indicate that vaccinated and convalescent people have some antibody protection against the B.1.1.7 variant but may still be at risk of infection with the B.1.351 strain. Nevertheless, two doses of the vaccine do boost neutralising antibody responses to these variants.

New SARS-CoV-2 variants, including the B.1.351 and B.1.1.7 strains, have spread to different countries, which has raised concerns about their ability to evade vaccines.

Olivier Schwartz and colleagues at the virus & immunity unit, department of virology, Institut Pasteur, CNRS UMR 3569-Paris, and Vaccine Research Institute-Créteil, France, isolated infectious B.1.1.7 and B.1.351 strains from infected people. They then tested the strains’ responses to antibodies collected from 19 vaccinated people up to 6 weeks after the first dose of the Pfizer vaccine, and from 58 unvaccinated people who had been infected with an earlier strain of the virus up to 9 months after symptoms first began.

The authors found that antibodies from convalescent patients were able to neutralize the B.1.1.7 strain, but were much less effective against the B.1.351 strain. There was a six-fold reduction in neutralizing activity, and 40% of the samples lacked any activity at all against the South African strain. Similarly, antibodies from vaccinated people were able to neutralise the B.1.1.7 strain, but had less of an effect against the B.1.351 strain. Although neutralizing activity increased after the second dose of vaccine, it remained 14 times lower against B.1.351 than against the D614G strain.

The study is of particular value because it used authentic viral strains rather than lab-engineered proxies. The authors argue that although the findings warrant further investigation, antibodies are just part of the immune system’s response to infectious viruses. Other elements of the immune system, such as the ability of T cells to attack infected cells, may be more cross-reactive against these faster-spreading variants.

 

Study details
Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies

Delphine Planas, Timothée Bruel, Ludivine Grzelak, Florence Guivel-Benhassine, Isabelle Staropoli, Françoise Porrot, Cyril Planchais, Julian Buchrieser, Maaran Michael Rajah, Elodie Bishop, Mélanie Albert, Flora Donati, Matthieu Prot, Sylvie Behillil, Vincent Enouf, Marianne Maquart, Mounira Smati-Lafarge, Emmanuelle Varon, Frédérique Schortgen, Layla Yahyaoui, Maria Gonzalez, Jérôme De Sèze, Hélène Péré, David Veyer, Aymeric Sève, Etienne Simon-Lorière, Samira Fafi-Kremer, Karl Stefic, Hugo Mouquet, Laurent Hocqueloux, Sylvie van der Werf, Thierry Prazuck, Olivier Schwartz

Published in Nature Medicine on 26 March 2021

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.

 

Nature Medicine study (Open access)

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