Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants

Emanuele Andreano, Ida Paciello, Giulia Piccini, Noemi Manganaro, Piero Pileri, Inesa Hyseni, Margherita Leonardi, Elisa Pantano, Valentina Abbiento, Linda Benincasa, Ginevra Giglioli, Concetta De Santi, Massimiliano Fabbiani, Ilaria Rancan, Mario Tumbarello, Francesca Montagnani, Claudia Sala, Emanuele Montomoli and Rino Rappuoli ()
Additional contact information
Emanuele Andreano: Fondazione Toscana Life Sciences
Ida Paciello: Fondazione Toscana Life Sciences
Giulia Piccini: VisMederi S.r.l
Noemi Manganaro: Fondazione Toscana Life Sciences
Piero Pileri: Fondazione Toscana Life Sciences
Inesa Hyseni: VisMederi S.r.l
Margherita Leonardi: VisMederi S.r.l
Elisa Pantano: Fondazione Toscana Life Sciences
Valentina Abbiento: Fondazione Toscana Life Sciences
Linda Benincasa: VisMederi Research S.r.l.
Ginevra Giglioli: VisMederi Research S.r.l.
Concetta De Santi: Fondazione Toscana Life Sciences
Massimiliano Fabbiani: Siena University Hospital
Ilaria Rancan: Siena University Hospital
Mario Tumbarello: Siena University Hospital
Francesca Montagnani: Siena University Hospital
Claudia Sala: Fondazione Toscana Life Sciences
Emanuele Montomoli: VisMederi S.r.l
Rino Rappuoli: Fondazione Toscana Life Sciences

Nature, 2021, vol. 600, issue 7889, 530-535

Abstract: Abstract The emergence of SARS-CoV-2 variants is jeopardizing the effectiveness of current vaccines and limiting the application of monoclonal antibody-based therapy for COVID-19 (refs. 1,2). Here we analysed the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to investigate the nature of the B cell and antibody response at the single-cell level. Almost 6,000 cells were sorted, over 3,000 cells produced monoclonal antibodies against the spike protein and more than 400 cells neutralized the original SARS-CoV-2 virus first identified in Wuhan, China. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants escaped almost 70% of these antibodies, while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part, this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in people who were convalescent and generated potent and broadly neutralizing antibodies. Our data suggest that people who are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control emerging SARS-CoV-2 variants.

Date: 2021
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DOI: 10.1038/s41586-021-04117-7

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