Liver and Bile

J Hepatol. 2023;78(5):1017–27

Luxenburger H, Reeg DB, Lang-Meli J, Reinscheid M, Eisner M, Bettinger D, Oberhardt V, Salimi Alizei E, Wild K, Graeser A, Karl V, Sagar, Emmerich F, Klein F, Panning M, Huzly D, Bengsch B, Boettler T, Elling R, Thimme R, Hofmann M, Neumann-Haefelin C

Boosting compromised SARS-CoV-2-specific immunity with mRNA vaccination in liver transplant recipients

Background and aims: Liver transplant recipients (LTRs) demonstrate a reduced response to COVID-19 mRNA vaccination; however, a detailed understanding of the interplay between humoral and cellular immunity, especially after a third (and fourth) vaccine dose, is lacking.
Methods: The authors longitudinally compared the humoral, as well as CD4+ and CD8+ T-cell, responses between LTRs (n = 24) and healthy controls (n = 19) after 3 (LTRs: n = 9–16; healthy controls: n = 9–14 per experiment) to 4 (LTRs: n = 4; healthy controls: n = 4) vaccine doses, including in-depth phenotypical and functional characterization.
Results: Compared to healthy controls, development of high antibody titers required a third vaccine dose in most LTRs, while spike-specific CD8+ T cells with robust recall capacity plateaued after the second vaccine dose, albeit with a reduced frequency and epitope repertoire compared to healthy controls. This overall attenuated vaccine response was linked to a reduced frequency of spike-reactive follicular T helper cells in LTRs.

Conclusion: Three doses of a COVID-19 mRNA vaccine induce an overall robust humoral and cellular memory response in most liver transplant recipients. Decisions regarding additional booster doses may thus be based on individual vaccine responses as well as evolution of novel variants of concern.

DOI:  10.1016/j.jhep.2023.02.007