Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

• Published in: bioRxiv
• Main Authors: Park, Young-Jun, Pinto, Dora, Walls, Alexandra C, Liu, Zhuoming, Marco, Anna De, Benigni, Fabio, Zatta, Fabrizia, Silacci-Fregni, Chiara, Bassi, Jessica, Sprouse, Kaitlin R, Addetia, Amin, Bowen, John E, Stewart, Cameron, Giurdanella, Martina, Saliba, Christian, Guarino, Barbara, Schmid, Michael A, Franko, Nicholas, Logue, Jennifer, Dang, Ha V, Hauser, Kevin, Iulio, Julia di, Rivera, William, Schnell, Gretja, Rajesh, Anushka, Zhou, Jiayi, Farhat, Nisar, Kaiser, Hannah, Montiel-Ruiz, Martin, Noack, Julia, Lempp, Florian A, Janer, Javier, Abdelnabi, Rana, Maes, Piet, Ferrari, Paolo, Ceschi, Alessandro, Giannini, Olivier, de Melo, Guilherme Dias, Kergoat, Lauriane, Bourhy, Hervé, Neyts, Johan, Soriaga, Leah, Purcell, Lisa A, Snell, Gyorgy, Whelan, Sean P J, Lanzavecchia, Antonio, Virgin, Herbert W, Piccoli, Luca, Chu, Helen, Pizzuto, Matteo Samuele, Corti, Davide, Veesler, David
• Format: Journal Article Paper
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 22.08.2022; Cold Spring Harbor Laboratory
• Edition: 1.4
• Subjects: Antibodies; Biotechnology; Immune imprinting; Immunological memory; Immunology; Lymphocytes B; Memory cells; Mucosa; Mutation; Patent applications; Plasma cells; Severe acute respiratory syndrome coronavirus 2; Vaccination
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2022.05.08.491108

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.