Antigenic sin and multiple breakthrough infectionsdrive converging evolution of COVID-19 neutralizingresponses

Cell Reports

Ida Paciello, Giulio Pierleoni, Elisa Pantano, Giada Antonelli, Piero Pileri, Giuseppe Maccari, Dario Cardamone, Giulia Realini, Federica Perrone, Martin Mayora Neto, Simone Pozzessere, Massimiliano Fabbiani, Francesca Panza, Ilaria Rancan, Mario Tumbarello, Francesca Montagnani, Duccio Medini, Piet Maes, Nigel Temperton, Etienne Simon-Loriere Olivier Schwartz, Rino Rappuoli, Emanuele Andreano

Summary

Understanding the evolution of the B cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is fundamental to design the next generation of vaccines and therapeutics. We longitudinally analyze at the single-cell level almost 900 neutralizing human monoclonal antibodies (nAbs) isolated from vaccinated people and from individuals with hybrid and super hybrid immunity (SH), developed after three mRNA vaccine doses and two breakthrough infections. The most potent neutralization and Fc functions against highly mutated variants belong to the SH cohort. Repertoire analysis shows that the original Wuhan antigenic sin drives the convergent expansion of the same B cell germlines in vaccinated and SH cohorts. Only Omicron breakthrough infections expand previously unseen germ lines and generate broadly nAbs by restoring IGHV3-53/3-66 germ lines. Our analyses find that B cells initially expanded by the original antigenic sin continue to play a fundamental role in the evolution of the immune response toward an evolving virus.

More information at DOI: https://doi.org/10.1016/j.celrep.2024.114645