B and T Cell Response after Third Dose of SARS-CoV2 Vaccine in Kidney Transplant Patients

Kidney transplant recipients (KTR) receiving immunosuppressive medication exhibit reduced immune responses after mRNA-based vaccination. In order to address this clinical challenge, a third vaccination for solid organ transplant recipients has recently become standard of care.

In the current study, we evaluate the effectiveness of a third vaccination dose of either heterologous ChAdOx1 (Vaxzevria) or homologous BNT162b2 (Comirnaty) in 25 KTR patients.

As per observations, the B and T cell response after a third vaccination with either ChAdOx1 or BNT162b2 in previously non-responding KTR showed an increase in anti-S1 IgG in 9/25 (36%) patients, 4/14 (28%) after homologous and 5/11 (45%) after heterologous vaccination. The overall prevalence of KTR patients displaying spike-specific CD4+ T cell responses was high (>90%) after the second and third inoculation with no significant changes of antigen reactive T cell frequencies. However, individuals who seroconverted after the third vaccination were characterized by significantly higher portions of antigen-reactive T cells when compared to non-responders.

Analysis of activation-associated markers revealed a significant drop of proliferating Ki67+ and activated PD1+ T cells after the third dose whereas no changes in specific memory/effector subset composition were noted. KTR patients showed significantly higher frequencies of IL-2 and IL-4 secretion as well as polyfunctional IFNγ+ TNFα+ IL-2+ T cells after the third dose.

Solid organ recipients receiving antimetabolite medication show a diminished immune response against SARS-CoV-2 vaccination. One potential strategy to improve responder rates is to reduce immunosuppression and especially antimetabolite treatment in patients with stable allograft function without previous episodes of rejection or pre-existing HLA immunization prior to vaccination. 

In conclusion, a third vaccination against SARS-CoV-2 leads to a serological response in a fraction of KTR, while the majority of patients still lack protective antibody titers. This lack of serological response can be explained by only marginal improvements in cellular protection among antigen specific B cells and T cells after a third vaccination. Alternative vaccination protocols are urgently needed to protect this at-risk group. 

Ref Link: https://www.medrxiv.org/content/10.1101/2021.08.12.21261966v1.full.pdf



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