Paper

Hybrid immunity improves B cell frequency, antibody potency and breadth against SARS-CoV-2 and variants of concern

Fabbiani, Massimiliano, Pantano, Elisa, Andreano, Emanuele, Paciello, Ida, Piccini, Giulia, Leonardi, Margherita, De Santi, Concetta, Rappuoli, Rino, Rancan, Ilaria, Pileri, Piero, Hyseni, Inesa, Benincasa, Linda, Tumbarello, Mario, Montagnani, Francesca, Sala, Claudia, Abbiento, Valentina, Giglioli, Ginevra, Manganaro, Noemi, Montomoli, Emanuele

2021

Overview

To understand the nature of the antibody response to SARS-CoV-2 vaccination, we analyzed at single cell level the B cell responses of five naïve and five convalescent people immunized with the BNT162b2 mRNA vaccine. Convalescents had higher frequency of spike protein specific memory B cells and by cell sorting delivered 3,532 B cells, compared with 2,352 from naïve people. Of these, 944 from naïve and 2,299 from convalescents produced monoclonal antibodies against the spike protein and 411 of them neutralized the original Wuhan SARS-CoV-2 virus. More than 75% of the monoclonal antibodies from naïve people lost their neutralization activity against the B.1.351 (beta) and B.1.1.248 (gamma) variants while this happened only for 61% of those from convalescents. The overall loss of neutralization was lower for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants, however it was always significantly higher in those of naïve people. In part this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in convalescents and generated potent and broadly neutralizing antibodies. Overall, vaccination of seropositive people increases the frequency of B cells encoding antibodies with high potency and that are not susceptible to escape by any of the four variants of concern. Our data suggest that people that are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control SARS-CoV-2 emerging variants. Competing Interest Statement Rino Rappuoli is an employee of GSK group of companies. EA, IP, NM, PP, EP, CDS, CS and RR 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.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Antibody response / Immunological memory / Immunology / Lymphocytes B / Memory cells / Monoclonal antibodies / mRNA / Patent applications / Severe acute respiratory syndrome coronavirus 2 / Spike protein / Vaccination