title: Induction of T lymphocyte responses to dengue virus by a candidate tetravalent live attenuated dengue virus vaccine.
abstract: Development of a safe and immunogenic tetravalent dengue virus (DV) vaccine has been designated as a priority by the World Health Organization. We characterized the T cell response to DV induced by a candidate live attenuated tetravalent DV vaccine as part of a phase I study. Proliferation and cytotoxic T lymphocyte (CTL) responses to multiple DV serotypes were detected in six of six and four of four subjects studied, respectively. Proliferation responses were higher to DV serotypes 1 and 3 than to serotypes 2 and 4. CTL responses were higher to DV serotypes 2 and 3 than to serotype 1, and included serotype cross-reactive responses. Production of interferon-gamma, but not IL-4, was observed in response to DV stimulation. This candidate vaccine is immunogenic for both CD4+ and CD8+ T lymphocytes. However, T cell responses to the four DV serotypes were not equivalent, suggesting that the vaccine could be further optimized.
authors.affiliation: Center for Infectious Disease and Vaccine Research, Rm. S5-326, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. alan.rothman@umassmed.edu
authors.forename: A L
authors.initials: AL
authors.lastname: Rothman
authors.forename: N
authors.initials: N
authors.lastname: Kanesa-thasan
authors.forename: K
authors.initials: K
authors.lastname: West
authors.forename: J
authors.initials: J
authors.lastname: Janus
authors.forename: J F
authors.initials: JF
authors.lastname: Saluzzo
authors.forename: F A
authors.initials: FA
authors.lastname: Ennis
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017077:Culture Media, Conditioned / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D003716:Dengue Virus / Q000276:immunology*; D014644:Genetic Variation; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017077:Culture Media, Conditioned; D016207:Cytokines; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma