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

View ORCID ProfileEmanuele Andreano, View ORCID ProfileIda Paciello, Giulio Pierleoni, View ORCID ProfileGiuseppe Maccari, Giada Antonelli, Valentina Abbiento, View ORCID ProfilePiero Pileri, Linda Benincasa, Ginevra Giglioli, View ORCID ProfileGiulia Piccini, View ORCID ProfileConcetta De Santi, View ORCID ProfileClaudia Sala, View ORCID ProfileDuccio Medini, View ORCID ProfileEmanuele Montomoli, View ORCID ProfilePiet Maes, View ORCID ProfileRino Rappuoli
doi: https://doi.org/10.1101/2022.08.04.502828
Emanuele Andreano
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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  • ORCID record for Emanuele Andreano
Ida Paciello
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Giulio Pierleoni
2VisMederi Research S.r.l., Siena, Italy
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Giuseppe Maccari
3Data Science for Health (DaScH) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Giada Antonelli
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Valentina Abbiento
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Piero Pileri
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Linda Benincasa
2VisMederi Research S.r.l., Siena, Italy
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Ginevra Giglioli
2VisMederi Research S.r.l., Siena, Italy
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Giulia Piccini
4VisMederi S.r.l, Siena, Italy
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Concetta De Santi
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Claudia Sala
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
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Duccio Medini
4VisMederi S.r.l, Siena, Italy
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Emanuele Montomoli
2VisMederi Research S.r.l., Siena, Italy
4VisMederi S.r.l, Siena, Italy
5Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy
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Piet Maes
6KU Leuven, Rega Institute, Department of Microbiology, Immunology and Transplantation, Laboratory of Clinical and Epidemiological Virology, Leuven, Belgium
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Rino Rappuoli
1Monoclonal Antibody Discovery (MAD) Lab, Fondazione Toscana Life Sciences, Siena, Italy
7Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy
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  • For correspondence: rino.r.rappuoli@gsk.com
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ABSTRACT

SARS-CoV-2 omicron BA.4 and BA.5, characterized by high transmissibility and ability to escape natural and vaccine induced immunity, are rampaging worldwide. To understand the escape mechanisms, we tested the neutralizing activity against omicron BA.4 and BA.5 of a panel of 482 human monoclonal antibodies that had been isolated from people who received two or three mRNA vaccine doses or from people that had been vaccinated after infection. None of the antibodies isolated after two vaccine doses neutralized omicron BA.4 and BA.5, while these variants were neutralized by approximately 15% of antibodies obtained from people that received three doses or had been vaccinated after infection. Remarkably, the antibodies isolated after three vaccine doses targeted mainly the receptor binding domain (RBD) Class 1/2 epitope region and were encoded by the IGHV1-69 and IGHV3-66 B cell germlines, while the antibodies isolated after infection recognized mostly the RBD Class 3 epitope region and the NTD, and were encoded by the IGHV2-5;IGHJ4-1 and IGHV1-24;IGHJ4-1 germlines. 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 COVID-19.

Competing Interest Statement

R.R. is an employee of GSK group of companies. E.A., I.P., V.A., P.P., C.D.S., C.S. and R.R. are listed as inventors of full-length human monoclonal antibodies described in Italian patent applications n. 102020000015754 filed on June 30th 2020, 102020000018955 filed on August 3rd 2020 and 102020000029969 filed on 4th of December 2020, and the international patent system number PCT/IB2021/055755 filed on the 28th of June 2021. All patents were submitted by Fondazione Toscana Life Sciences, Siena, Italy. R.D.F. is a consultant for Moderna on activities not related to SARS-CoV-2. Remaining authors have no competing interests to declare.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 05, 2022.
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mRNA vaccines and hybrid immunity use different B cell germlines to neutralize 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, Rino Rappuoli
bioRxiv 2022.08.04.502828; doi: https://doi.org/10.1101/2022.08.04.502828
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mRNA vaccines and hybrid immunity use different B cell germlines to neutralize 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, Rino Rappuoli
bioRxiv 2022.08.04.502828; doi: https://doi.org/10.1101/2022.08.04.502828

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