B cell analyses after SARS-CoV-2 mRNA third vaccination reveals a hybrid immunity like antibody response
Emanuele Andreano, Ida Paciello, Giulio Pierleoni, Giulia Piccini, Valentina Abbiento, Giada Antonelli, Piero Pileri, Noemi Manganaro, Elisa Pantano, Giuseppe Maccari, Silvia Marchese, Lorena Donnici, Linda Benincasa, Ginevra Giglioli, Margherita Leonardi, Concetta De Santi, Massimiliano Fabbiani, Ilaria Rancan, Mario Tumbarello, Francesca Montagnani, Claudia Sala, Duccio Medini, Raffaele De Francesco, Emanuele Montomoli, Rino Rappuoli
Abstract
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.