B cell analyses after SARS-CoV-2 mRNA third vaccination reveals a hybrid immunity like antibody response

• Published in: Nature communications 2023-01, Vol.14 (1), p.53-9, Article 53
• Main Authors: Andreano, Emanuele, Paciello, Ida, Pierleoni, Giulio, Piccini, Giulia, Abbiento, Valentina, Antonelli, Giada, Pileri, Piero, Manganaro, Noemi, Pantano, Elisa, Maccari, Giuseppe, Marchese, Silvia, Donnici, Lorena, Benincasa, Linda, Giglioli, Ginevra, Leonardi, Margherita, De Santi, Concetta, Fabbiani, Massimiliano, Rancan, Ilaria, Tumbarello, Mario, Montagnani, Francesca, Sala, Claudia, Medini, Duccio, De Francesco, Raffaele, Montomoli, Emanuele, Rappuoli, Rino
• Format: Article
• Language: English
• Subjects: 13/1; 13/109; 13/31; 38/23; 38/77; 38/88; 49/47; 631/250/2152/2040; 631/250/2152/2153/1291; 631/250/2152/2497; 631/326/590/2293; 631/326/596/4130; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Antibody Formation; Antibody response; B-Lymphocytes - immunology; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Evolution; Humanities and Social Sciences; Humans; Immunity; Immunization; Immunological memory; Lymphocytes B; Memory cells; mRNA; multidisciplinary; Neutralization; Neutralizing; SARS-CoV-2 - genetics; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - genetics; Spike protein; Vaccination; Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-35781-6

The continuous evolution of SARS-CoV-2 generated highly mutated variants able to escape natural and vaccine-induced primary immunity. The administration of a third mRNA vaccine dose induces a secondary response with increased protection. Here we investigate the longitudinal evolution of the neutralizing antibody response in four donors after three mRNA doses at single-cell level. We sorted 4100 spike protein specific memory B cells identifying 350 neutralizing antibodies. The third dose increases the antibody neutralization potency and breadth against all SARS-CoV-2 variants as observed with hybrid immunity. However, the B cell repertoire generating this response is different. The increases of neutralizing antibody responses is largely due to the expansion of B cell germlines poorly represented after two doses, and the reduction of germlines predominant after primary immunization. Our data show that different immunization regimens induce specific molecular signatures which should be considered while designing new vaccines and immunization strategies. SARS-CoV-2 vaccines and infection induce antibody responses but the evolution of subsequent variants has resulted in the development of escape mutants. Here the authors characterise, at single cell level, the antibody response in donors after a third dose of SARS-CoV-2 mRNA vaccination and show difference in breadth, neutralisation and molecular signature according to the vaccination regimen used.