PT  - JOURNAL ARTICLE
AU  - Emanuele Andreano
AU  - Ida Paciello
AU  - Giulio Pierleoni
AU  - Giuseppe Maccari
AU  - Giada Antonelli
AU  - Valentina Abbiento
AU  - Piero Pileri
AU  - Linda Benincasa
AU  - Ginevra Giglioli
AU  - Giulia Piccini
AU  - Concetta De Santi
AU  - Claudia Sala
AU  - Duccio Medini
AU  - Emanuele Montomoli
AU  - Piet Maes
AU  - Rino Rappuoli
TI  - mRNA vaccines and hybrid immunity use different B cell germlines to neutralize Omicron BA.4 and BA.5
AID  - 10.1101/2022.08.04.502828
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.04.502828
4099  - http://biorxiv.org/content/early/2022/08/05/2022.08.04.502828.short
4100  - http://biorxiv.org/content/early/2022/08/05/2022.08.04.502828.full
AB  - 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 StatementR.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.