Three doses of the messenger RNA vaccine BNT162b2 (Pfizer–BioNTech) was given to 101 solid organ transplant recipients. The group included 78 kidney-transplant recipients, 12 liver-transplant recipients, 8 lung-transplant or heart-transplant recipients, and 3 pancreas-transplant recipients. The first two doses were given 1 month apart, and the third dose was administered 61±1 days after the second dose. The prevalence of anti–SARS-CoV-2 antibodies was 0% (95% confidence interval [CI], 0 to 4; 0 of 101 patients) before the first dose, 4% (95% CI, 1 to 10; 4 of 101 patients) before the second dose, 40% (95% CI, 31 to 51; 40 of 99 patients) before the third dose, and 68% (95% CI, 58 to 77; 67 of 99 patients) 4 weeks after the third dose. Patients who did not have an antibody response were older, had a higher degree of immunosuppression, and had a lower estimated glomerular filtration rate than patients who had an antibody response. This study showed that administration of a third dose of the BNT162b2 vaccine to solid-organ transplant recipients significantly improved the immunogenicity of the vaccine, with no cases of Covid-19 reported in any of the patients. However, a large proportion of the patients remain at risk for Covid-19. Barrier measures should be maintained, and vaccination of the relatives of these patients should be encouraged.

This study examined antigen-specific B cell responses in peripheral blood (n=41) and draining lymph nodes (LNs) in 14 individuals who received two doses of BNT162b2. By examining fine needle aspirates (FNAs) of draining axillary LNs, the study identified germinal center (GC) B cells that bound S protein in all participants sampled after primary immunization. Remarkably, high frequencies of S-binding GC B cells and PBs were sustained in these draining LNs for at least twelve weeks after the booster immunization. S-binding GC B cell-derived monoclonal antibodies predominantly targeted the receptor binding domain of the S protein, with fewer clones binding to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. The latter cross-reactive B cell clones had higher levels of somatic hypermutation compared to those that only recognized SARS-CoV-2 S protein, suggesting a memory B cell origin. This study demonstrates that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent GC B cell response, enabling the generation of robust humoral immunity.

This study analyzed humoral and B cell responses of 35 healthy control (HC), 44 dialysis patients (DP) and 40 kidney transplant recipients (KTR). Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG and IgA positivity in 70.5% and 68.2%, respectively. In contrast, KTR did not develop IgG responses except one patient who had a prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. These data indicated that immunosuppression resulted in impaired protective immunity after mRNA vaccination, including Ig induction with corresponding generation of plasmablasts and memory B cells.