Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees

Emanuele Andreano, Ida Paciello, Silvia Marchese, Lorena Donnici, Giulio Pierleoni, Giulia Piccini, Noemi Manganaro, Elisa Pantano, Valentina Abbiento, Piero Pileri, Linda Benincasa, Ginevra Giglioli, Margherita Leonardi, Piet Maes, Concetta De Santi, Claudia Sala, Emanuele Montomoli, Raffaele De Francesco and Rino Rappuoli ()
Additional contact information
Emanuele Andreano: Fondazione Toscana Life Sciences
Ida Paciello: Fondazione Toscana Life Sciences
Silvia Marchese: University of Milan
Lorena Donnici: INGM, Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”
Giulio Pierleoni: VisMederi S.r.l
Giulia Piccini: VisMederi S.r.l
Noemi Manganaro: Fondazione Toscana Life Sciences
Elisa Pantano: Fondazione Toscana Life Sciences
Valentina Abbiento: Fondazione Toscana Life Sciences
Piero Pileri: Fondazione Toscana Life Sciences
Linda Benincasa: VisMederi Research S.r.l.
Ginevra Giglioli: VisMederi Research S.r.l.
Margherita Leonardi: VisMederi S.r.l
Piet Maes: Laboratory of Clinical and Epidemiological Virology
Concetta De Santi: Fondazione Toscana Life Sciences
Claudia Sala: Fondazione Toscana Life Sciences
Emanuele Montomoli: VisMederi S.r.l
Raffaele De Francesco: University of Milan
Rino Rappuoli: Fondazione Toscana Life Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract SARS-CoV-2 vaccines, administered to billions of people worldwide, mitigate the effects of the COVID-19 pandemic, however little is known about the molecular basis of antibody cross-protection to emerging variants, such as Omicron BA.1, its sublineage BA.2, and other coronaviruses. To answer this question, 276 neutralizing monoclonal antibodies (nAbs), previously isolated from seronegative and seropositive donors vaccinated with BNT162b2 mRNA vaccine, were tested for neutralization against the Omicron BA.1 and BA.2 variants, and SARS-CoV-1 virus. Only 14.2, 19.9 and 4.0% of tested antibodies neutralize BA.1, BA.2, and SARS-CoV-1 respectively. These nAbs recognize mainly the SARS-CoV-2 receptor binding domain (RBD) and target Class 3 and Class 4 epitope regions on the SARS-CoV-2 spike protein. Interestingly, around 50% of BA.2 nAbs did not neutralize BA.1 and among these, several targeted the NTD. Cross-protective antibodies derive from a variety of germlines, the most frequents of which were the IGHV1-58;IGHJ3-1, IGHV2-5;IGHJ4-1 and IGHV1-69;IGHV4-1. Only 15.6, 20.3 and 7.8% of predominant gene-derived nAbs elicited against the original Wuhan virus cross-neutralize Omicron BA.1, BA.2 and SARS-CoV-1 respectively. Our data provide evidence, at molecular level, of the presence of cross-neutralizing antibodies induced by vaccination and map conserved epitopes on the S protein that can inform vaccine design.

Date: 2022
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DOI: 10.1038/s41467-022-31115-8

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