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.

Takuto Nogimori, Yuta Nagatsuka, Shogo Kobayashi, Hirotomo Murakami, Yuji Masuta, Koichiro Suzuki, Yoshito Tomimaru, Takehiro Noda, Hirofumi Akita, Shokichi Takahama, Yasuo Yoshioka, Yuichiro Doki, Hidetoshi Eguchi, Takuya Yamamoto