SARS-CoV-2-specific B cell responses in non-draining lymph nodes and antibody functionalities in immunized end-stage renal disease patients.

The degree to which COVID-19 vaccination induces B-cell responses in non-draining lymph nodes (LNs) is unknown. Therefore, non-draining iliac LNs and paired peripheral blood (PB) of end-stage renal disease patients were retrieved during kidney transplantation. Prior, participants received two (n = 5), three (n = 4), or four mRNA-based vaccinations (n = 3) and 4 patients had previous SARS-CoV-2 infection, of whom 2 received two vaccinations. Samples were obtained on average 79 days post-vaccination and 162 days post-infection. Spike S1(S)-binding B-cells were detected in LNs and PB 210 and 243 days after vaccination and infection, respectively. These B-cells predominantly consisted of IgG-secreting plasmablasts. In serum, a decreased IgG1/IgG4 ratio upon repeated vaccination, coherent with high fractions of S-binding IgG4 in LNs, correlated with reduced Fc-mediated functionalities but not neutralization capacity. Thus, mRNA-based COVID-19 vaccination could induce a systemic and long-lived, highly functional virus-specific B-cell response. Understanding IgG4 skewing is important for future vaccination strategies, especially in immunocompromised populations.