Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections

• Published in: Cell host & microbe Vol. 30; no. 3; pp. 400 - 408.e4
• Main Authors: Terreri, Sara, Piano Mortari, Eva, Vinci, Maria Rosaria, Russo, Cristina, Alteri, Claudia, Albano, Christian, Colavita, Francesca, Gramigna, Giulia, Agrati, Chiara, Linardos, Giulia, Coltella, Luana, Colagrossi, Luna, Deriu, Gloria, Ciofi Degli Atti, Marta, Rizzo, Caterina, Scarsella, Marco, Brugaletta, Rita, Camisa, Vincenzo, Santoro, Annapaola, Roscilli, Giuseppe, Pavoni, Emiliano, Muzi, Alessia, Magnavita, Nicola, Scutari, Rossana, Villani, Alberto, Raponi, Massimiliano, Locatelli, Franco, Perno, Carlo Federico, Zaffina, Salvatore, Carsetti, Rita
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.03.2022; The Authors. Published by Elsevier Inc
• Subjects: Antibodies, Viral; BNT162 Vaccine; breakthrough infections; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines; Humans; memory B cells; mRNA vaccine; mRNA Vaccines; mucosal immunity; salivary IgA; SARS-CoV-2; Vaccination; Vaccines, Synthetic; waning immunity; COVID-19; SARS-CoV-2; breakthrough infections; waning immunity; salivary IgA; memory B cells; mucosal immunity; mRNA vaccine
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2022.01.003

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3–4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen. [Display omitted] •Anti-Spike antibodies decline 9 months after vaccination, but memory B cells increase•Breakthrough infections are not associated with waning immunity•Breakthrough infections lead to increase of specific antibodies in serum and saliva•Parenterally administered vaccines do not generate mucosal immunity Terreri, Piano Mortari, and colleagues show that memory B cells persist and increase months after SARS-CoV-2 vaccination even if specific antibodies physiologically decline. Health care workers with breakthrough infections had no signs of waning immunity, as memory B cells produce high levels of specific antibodies in the serum and saliva.