In vitro studies of the impact of maribavir on CMV-specific cellular immune responses

• The most commonly used CMV drug ganciclovir has suppressive effects on T cell function.
• Maribavir exhibits a low potential to suppress CMV-specific T cell function.
• This may support higher doses for prophylactic indication than originally proposed.

BackgroundGanciclovir has demonstrated immunosuppressive effects in vitro which may lead to delayed cytomegalovirus (CMV)-specific immune reconstitution when the drug is given prophylactically. Maribavir is a new and more potent anti-CMV drug that is under evaluation for therapeutic use in transplant recipients.ObjectivesThe objective of this study was to evaluate the potential effect of maribavir on CMV-specific T cell function in comparison to ganciclovir.Study designIn ten immunocompetent CMV seropositive donors, maribavir and ganciclovir were compared over a broad range of concentrations (0.2–500 μM) regarding their effects on lymphoproliferation, CMV-specific CD4+ and CD8+ cytokine expression, T cell multifunctionality, degranulation and apoptosis.ResultsMaribavir inhibited lymphocyte proliferation at concentrations of 50 μM and above, however, cytokine expression, cellular degranulation and multifunctionality of CD4+ and CD8+ T cells in response to CMV lysate and pp65 peptide mix were not impaired except at the highest concentration of 500 μM. Ganciclovir inhibited lymphoproliferative responses starting at 10 μM. As with maribavir, other cellular responses following stimulation with CMV lysate and pp65 peptide mix were only impaired at the highest concentration of 500 μM of ganciclovir. Neither maribavir nor ganciclovir showed induction of lymphocyte apoptosis.ConclusionsMaribavir exhibits a low potential to suppress CMV-specific T cell function. This finding supports the use of higher doses in the prophylactic setting than originally proposed.