Humoral and cellular immune responses to COVID-19 mRNA vaccines in immunosuppressed liver transplant recipients

Background: Liver transplant recipients (LTRs) are at high risk of severe COVID-19 due to immunosuppression and comorbidities and show reduced responsiveness to mRNA vaccines compared with healthy donors (HDs), but the status of humoral and cellular immune memory is unclear. Methods: We longitudinally sampled plasma and PBMCs from HDs (n = 44) and LTRs (n = 54) vaccinated with BNT162b2 or mRNA-1273 and quantified anti–receptor-binding domain (RBD) IgG and spike-specific CD4+ and CD8+ T-cell responses. Results: Anti-RBD IgG induction was weaker in LTRs than HDs. Use of multiple immunosuppressive drugs was associated with lower antibody titers than calcineurin inhibitor (CNI) monotherapy and limited CD4+ T-cell responses. A third vaccine dose improved spike-specific CD4+ T-cell and antibody responses. Spike-specific CD8+ T cells induced by mRNA vaccines were quantitatively, but not qualitatively, limited in LTRs, and both CD4+ and CD8+ T cells recognized common Omicron sublineages. A third vaccination did not boost spike-specific memory CD8+ T-cell responses in either HDs or LTRs. Conclusions: mRNA vaccination elicits humoral and spike-specific CD4+ T-cell responses in LTRs, while memory CD8+ T-cell responses are not boosted by a third dose. A third mRNA vaccination may help prevent severe COVID-19 in LTRs, though further work is needed to enhance CD8+ T-cell responses in both LTRs and HDs.