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

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.

• Authors: 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, Rino Rappuoli
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 3375 (06 13 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35697673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• COVID-19 Vaccines
• Epitopes
• RNA, Messenger
• Spike Glycoprotein, Coronavirus
• Vaccines, Synthetic
• mRNA Vaccines
• spike protein, SARS-CoV-2
• BNT162 Vaccine

Topics

• Antibodies, Neutralizing
• Antibodies, Viral
• BNT162 Vaccine
• COVID-19 (prevention & control)
• COVID-19 Vaccines
• Epitopes (genetics)
• Humans
• Neutralization Tests
• Pandemics (prevention & control)
• RNA, Messenger (genetics)
• SARS-CoV-2 (genetics)
• Spike Glycoprotein, Coronavirus (genetics)
• Vaccines, Synthetic
• mRNA Vaccines