RT Journal Article
SR Electronic
T1 Hybrid immunity improves B cell frequency, antibody potency and breadth against SARS-CoV-2 and variants of concern
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.08.12.456077
DO 10.1101/2021.08.12.456077
A1 Emanuele Andreano
A1 Ida Paciello
A1 Giulia Piccini
A1 Noemi Manganaro
A1 Piero Pileri
A1 Inesa Hyseni
A1 Margherita Leonardi
A1 Elisa Pantano
A1 Valentina Abbiento
A1 Linda Benincasa
A1 Ginevra Giglioli
A1 Concetta De Santi
A1 Massimiliano Fabbiani
A1 Ilaria Rancan
A1 Mario Tumbarello
A1 Francesca Montagnani
A1 Claudia Sala
A1 Emanuele Montomoli
A1 Rino Rappuoli
YR 2021
UL http://biorxiv.org/content/early/2021/08/12/2021.08.12.456077.abstract
AB 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 StatementRino 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.