LAUSR

Kidney transplant recipients (KTRs) are highly vulnerable to COVID‐19. An intensified scheme of vaccination offers short‐term protection to the 50%–75% of KTRs able to develop a germinal center reaction, required for the generation of neutralizing titers of antibodies (NAbs). However, the duration of this vaccinal protection is unknown. In‐depth longitudinal analysis of the immune response to vaccination of 33 KTRs demonstrates that the low peak of IgGs, the progressive decline in antibody titers, and the emergence of a variant of concerns (VOC) of SARS‐CoV2, synergize to let 2/3 of responders to vaccine without NAbs after only a few months. Yet, a retrospective study of an independent cohort of 274 KTRs, revealed that the risk of severe COVID‐19 in the latter was low, similar to that of patients with serum neutralizing capacity against VOC. Our work links this late vaccine protection with the presence of memory B cells, which are generated during the initial vaccine‐induced germinal center reaction, have a wide repertoire directed against conserved spike epitopes, and rapidly differentiate into IgG‐producing plasma cells upon antigenic rechallenge. We conclude that in contrast with a serological layer that goes fading rapidly, the cellular layer of humoral memory provides an efficient long‐term protection against VOC to KTRs. This illustration of the complementary roles of the two layers of the humoral memory has implications in immunopathology beyond the COVID‐19 in KTRs.