Temporary hold of mycophenolate boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients

Abstract

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept-treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo activated PD1+ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.

Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients

“…In a preprint format, Schrezenmeier et al reported the result of a study assessing a fourth dose BNT162b2 vaccine in 29 kidney transplant recipients who did not seroconvert with the three first doses of the vaccine and were on MMF (152). The fourth dose was administered 4-7 days after MMF hold and MMF was paused until day 28-35 after vaccination.…”

Declining Course of Humoral Immune Response in Initially Responding Kidney Transplant Recipients after Repeated SARS-CoV-2 Vaccination

“…Kidney transplant recipients treated and followed at our institution received repeated doses of SARS-CoV-2 vaccines in case of sustained non-response to vaccination against SARS-CoV-2 (14). Data from up to five doses of vaccine were included in this analysis.…”

“…A third vaccination was recommended early on for KTR in order to increase immune response (13). Further, repeated vaccinations under modulated immunosuppression effectively increase protection, yet a substantial number of patients does not reach protective antibody levels (14,15).…”

Serological Response to Three, Four and Five Doses of SARS-CoV-2 Vaccine in Kidney Transplant Recipients

“…11 T cell response over time only changes at a functional level, never reaching the level of healthy individuals. 12,13 In summary the poor T cell response in combination with an impaired humoral response offered only a limited protection from infection and a severe course of COVID-19. 14…”

“…11 T cell response over time only changes at a functional level, never reaching the level of healthy individuals. 12,13 In summary the poor T cell response in combination with an impaired humoral response offered only a limited protection from infection and a severe course of COVID-19. 14 The question therefore arises about optimal management of non-responding patients and in particular whether repeated vaccinations increase serological response rates.…”