title: In vitro studies of the impact of maribavir on CMV-specific cellular immune responses.
abstract: BACKGROUND
  Ganciclovir 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.
  
  
  OBJECTIVE
  The objective of this study was to evaluate the potential effect of maribavir on CMV-specific T cell function in comparison to ganciclovir.
  
  
  METHODS
  In ten immunocompetent CMV seropositive donors, maribavir and ganciclovir were compared over a broad range of concentrations (0.2-500μM) regarding their effects on lymphoproliferation, CMV-specific CD4+ and CD8+ cytokine expression, T cell multifunctionality, degranulation and apoptosis.
  
  
  RESULTS
  Maribavir inhibited lymphocyte proliferation at concentrations of 50μM 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 500μM. Ganciclovir inhibited lymphoproliferative responses starting at 10μM. As with maribavir, other cellular responses following stimulation with CMV lysate and pp65 peptide mix were only impaired at the highest concentration of 500μM of ganciclovir. Neither maribavir nor ganciclovir showed induction of lymphocyte apoptosis.
  
  
  CONCLUSIONS
  Maribavir 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.
authors.affiliation: From the Vaccine and Infectious Disease and Clinical Research Divisions, Fred Hutchinson Cancer Research Center, and the Department of Medicine, University of Washington, Seattle, WA, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stachel
authors.affiliation: From the Vaccine and Infectious Disease and Clinical Research Divisions, Fred Hutchinson Cancer Research Center, and the Department of Medicine, University of Washington, Seattle, WA, United States.
authors.forename: Terry
authors.initials: T
authors.lastname: Stevens-Ayers
authors.affiliation: From the Vaccine and Infectious Disease and Clinical Research Divisions, Fred Hutchinson Cancer Research Center, and the Department of Medicine, University of Washington, Seattle, WA, United States. Electronic address: mboeckh@fredhutch.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000187:drug effects / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control; D015774:Ganciclovir / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007121:Immunocompetence / Q000187:drug effects; D007159:Immunologic Tests; D012263:Ribonucleosides / Q000008:administration & dosage / Q000627:therapeutic use*; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D015774:Ganciclovir; D012263:Ribonucleosides; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole
keywords: Ganciclovir; Maribavir; T cell responses