title: The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.
abstract: A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines.
authors.affiliation: Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Alan M
authors.identifier: 0000-0003-0632-8296
authors.initials: AM
authors.lastname: Watson
authors.affiliation: Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: L K Metthew
authors.initials: LK
authors.lastname: Lam
authors.affiliation: Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: William B
authors.initials: WB
authors.lastname: Klimstra
authors.affiliation: Center for Vaccine Research, Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kate D
authors.initials: KD
authors.lastname: Ryman
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D056724:Immunity, Humoral / Q000276:immunology*; D051379:Mice; D016133:Polymerase Chain Reaction; D014613:Vaccines, Attenuated / Q000276:immunology; D015004:Yellow Fever / Q000276:immunology*; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D014613:Vaccines, Attenuated; D022341:Yellow Fever Vaccine