Persistent B-Cell Memory After SARS-CoV-2 Vaccination is Functional During Breakthrough Infections

Abstract

Breakthrough infections in fully vaccinated HCWs are considered a consequence of waning immunity. Serum antibodies represent the most visible and measurable outcome of vaccine-induced B-cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, thus preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and in vivo functional B-cell memory against SARS-CoV-2 3, 6 and 9 months after the second dose.We observed the physiological decline of SARS-CoV-2 specific antibodies months after vaccination. By contrast, 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.

Funding Information: Italian Ministry of Health COVID-2020-12371817 grant and Ricerca Corrente 2021 “5 per mille”.

Declaration of Interests: All authors declare no competing interests.

Ethics Approval Statement: Ethics Committee of Bambino Gesù Children Hospital, Rome, Italy, Ethical approved the study. The study was performed in accordance with the Good Clinical Practice guidelines, the International Conference on Harmonization guidelines, and the most recent version of the Declaration of Helsinki.

Keywords: SARS-CoV-2 vaccine, Memory B cells, serum antibodies, waning immunity, breakthrough infections, healthcare workers, salivary IgA.