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 and Rino Rappuoli ()
Additional contact information
Emanuele Andreano: Fondazione Toscana Life Sciences
Ida Paciello: Fondazione Toscana Life Sciences
Giulio Pierleoni: VisMederi Research S.r.l.
Giulia Piccini: VisMederi S.r.l
Valentina Abbiento: Fondazione Toscana Life Sciences
Giada Antonelli: Fondazione Toscana Life Sciences
Piero Pileri: Fondazione Toscana Life Sciences
Noemi Manganaro: Fondazione Toscana Life Sciences
Elisa Pantano: Fondazione Toscana Life Sciences
Giuseppe Maccari: Fondazione Toscana Life Sciences
Silvia Marchese: University of Milan
Lorena Donnici: INGM, Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”
Linda Benincasa: VisMederi Research S.r.l.
Ginevra Giglioli: VisMederi Research S.r.l.
Margherita Leonardi: VisMederi Research S.r.l.
Concetta De Santi: Fondazione Toscana Life Sciences
Massimiliano Fabbiani: Siena University Hospital
Ilaria Rancan: Siena University Hospital
Mario Tumbarello: Siena University Hospital
Francesca Montagnani: Siena University Hospital
Claudia Sala: Fondazione Toscana Life Sciences
Duccio Medini: Fondazione Toscana Life Sciences
Raffaele De Francesco: University of Milan
Emanuele Montomoli: VisMederi Research S.r.l.
Rino Rappuoli: Fondazione Toscana Life Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-9

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-022-35781-6

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