Journal
JCI INSIGHT
Volume 7, Issue 9, Pages -Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.157836
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Funding
- Federal Ministry of Education and Research grant (BCOVIT) [01KI20161]
- Charite-Universitatsmedizin Berlin
- Berlin Institute of Health
- German Society of Rheumatology
- Sonnenfeldstiftung Berlin, Germany
- Deutsche Forschungsgemeinschaft [Do491/7-5, Do491/10-2, Do491/11-1, Transregio 130 TP24, KO-2270/71, KO-2270/4-1]
- Chiesi GmbH
- COLCIENCIAS scholarship [727]
- Ministry for Science, Research and Arts of Baden-Wurttemberg, Germany
- European Commission (HORIZON2020 Project SUPPORT-E) [101015756]
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Transplant recipients may have impaired immunity after SARS-CoV-2 vaccination due to immunosuppression caused by mycophenolate (MPA). Temporary MPA hold has been shown to greatly improve the outcomes of booster vaccination in these patients.
Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, 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%) calcineurin inhibitor-treated patients responded, but only 1/4 belatacept-treated patients responded. In line with humoral responses. counts and relative frequencies of spike receptor binding domain-specific (RBD-specific) B cells were markedly 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 programmed cell death 1-positive T cells significantly increased after revaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, antimetabolite hold augmented all arms of immunity during booster vaccination. These data suggest further studies of antimetabolite hold in kidney transplant recipients.
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