Humoral and Cellular Immune Responses to COVID-19 Mrna Vaccines in Immunosuppressed Liver Transplant Recipients

Background Liver transplant recipients (LTRs) are at a high risk of severe COVID-19 owing to immunosuppression and comorbidities. LTRs are less responsive to mRNA vaccines than healthy donors (HDs) or other immunosuppressed patients. However, the disruption mechanism in humoral and cellular immune memory responses is unclear. Methods We longitudinally collected peripheral blood mononuclear cells and plasma samples from HDs ( n = 44) and LTRs ( n = 54) who received BNT162b2 or mRNA-1273 vaccines. We measured the levels of anti-receptor-binding domain (RBD) antibodies and spike-specific CD4 + and CD8 + T-cell responses. Results Here, we show that the induction of anti-RBD IgG was weaker in LTRs than in HDs. The use of multiple immunosuppressive drugs is associated with lower antibody titers than only calcineurin inhibitor, and limits the induction of CD4 + T-cell responses. However, spike-specific CD4 + T-cell and antibody responses improved with a third vaccination. Furthermore, mRNA vaccine-induced spike-specific CD8 + T cells are quantitatively, but not qualitatively, limited to LTRs. Both CD4 + and CD8 + T cells react to omicron sublineages, regardless of the presence in HDs or LTRs. However, there is no boosting effect of spike-specific memory CD8 + T-cell responses after a third vaccination in HDs or LTRs. Conclusions The third mRNA vaccination improves both humoral responses and spike-specific CD4 + T-cell responses in LTRs but provides no booster effect for spike-specific memory CD8 + T-cell responses. A third mRNA vaccination could be helpful in LTRs to prevent severe COVID-19, although further investigation is required to elicit CD8 + T-cell responses in LTRs and HDs.