B and T cell responses after a third dose of SARS-CoV-2 vaccine in Kidney Transplant Recipients

Abstract

Background: Accumulating evidence suggests that solid organ transplant recipients, as opposed to the general population, show strongly impaired responsiveness towards standard SARS-CoV-2 mRNA-based vaccination, demanding alternative strategies for protection of this vulnerable group. Methods: In line with recent recommendations, a third dose of either heterologous ChAdOx1 (AstraZeneca) or homologous BNT162b2 (BioNTech) was administered to 25 kidney transplant recipients (KTR) without humoral response after 2 doses of BNT162b2, followed by analysis of serological responses and vaccine-specific B- and T-cell immunity. Results: 9/25 (36%) KTR under standard immunosuppressive treatment seroconverted until day 27 after the third vaccination, while one patient developed severe COVID-19 infection immediately after vaccination. Cellular analysis seven days after the third dose showed significantly elevated frequencies of viral spike protein receptor binding domain specific B cells in humoral responders as compared to non-responders. Likewise, portions of spike-reactive CD4+ T helper cells were significantly elevated in seroconverting patients. Furthermore, overall frequencies of IL-2+, IL-4+ and polyfunctional CD4+ T cells significantly increased after the third dose, whereas memory/effector differentiation remained unaffected. Conclusions: Our data suggest that a fraction of transplant recipients benefits from triple vaccination, where seroconversion is associated with quantitative and qualitative changes of cellular immunity. At the same time, the study highlights that modified vaccination approaches for immunosuppressed patients still remain an urgent medical need.

Balancing B cell responses to the allograft: implications for vaccination

“…Future studies will need to investigate whether the defect is at the level of T cell activation or T cell help. Work in adult kidney transplant recipients has demonstrated additional vaccine doses can induce a functional maturation of vaccine-reactive T cells with significantly higher frequencies of IL-2 and IL-4 secreting and polyfunctional T cells being seen after a third dose ( 81 ).…”

Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

“…and T cells during SARS-CoV-2 vaccination is not fully understood, as humoral and T cell immunity appear to depend on B cell counts before vaccination. (6) In addition, data from immunocompromised kidney transplant patients show that T cell activity after vaccination correlates with the magnitude of the antibody response, (7) while high T cell activity has been observed in B cell depleted patients after immunisation. (8) Sera from vaccinated healthy individuals show only limited neutralisation capacity against Omicron (B.1.1.529) VOC.…”