mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5

Emanuele Andreano, Ida Paciello, Giulio Pierleoni, Giuseppe Maccari, Giada Antonelli, Valentina Abbiento, Piero Pileri, Linda Benincasa, Ginevra Giglioli, Giulia Piccini, Concetta De Santi, Claudia Sala, Duccio Medini, Emanuele Montomoli, Piet Maes and Rino Rappuoli ()
Additional contact information
Emanuele Andreano: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Ida Paciello: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Giulio Pierleoni: VisMederi Research S.r.l.
Giuseppe Maccari: Data Science for Health (DaScH) Lab, Fondazione Toscana Life Sciences
Giada Antonelli: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Valentina Abbiento: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Piero Pileri: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Linda Benincasa: VisMederi Research S.r.l.
Ginevra Giglioli: VisMederi Research S.r.l.
Giulia Piccini: VisMederi S.r.l
Concetta De Santi: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Claudia Sala: Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences
Duccio Medini: Data Science for Health (DaScH) Lab, Fondazione Toscana Life Sciences
Emanuele Montomoli: VisMederi Research S.r.l.
Piet Maes: Laboratory of Clinical and Epidemiological Virology
Rino Rappuoli: University of Siena

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: Abstract Severe acute respiratory syndrome 2 Omicron BA.4 and BA.5 are characterized by high transmissibility and ability to escape natural and vaccine induced immunity. Here we test the neutralizing activity of 482 human monoclonal antibodies isolated from people who received two or three mRNA vaccine doses or from people vaccinated after infection. The BA.4 and BA.5 variants are neutralized only by approximately 15% of antibodies. Remarkably, the antibodies isolated after three vaccine doses target mainly the receptor binding domain Class 1/2, while antibodies isolated after infection recognize mostly the receptor binding domain Class 3 epitope region and the N-terminal domain. Different B cell germlines are used by the analyzed cohorts. The observation that mRNA vaccination and hybrid immunity elicit a different immunity against the same antigen is intriguing and its understanding may help to design the next generation of therapeutics and vaccines against coronavirus disease 2019.

Date: 2023
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DOI: 10.1038/s41467-023-37422-y

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