title: Vaccine-induced measles virus-specific T cells do not prevent infection or disease but facilitate subsequent clearance of viral RNA.
abstract: Infection with wild-type measles virus (MeV) induces lifelong protection from reinfection, and parenteral delivery of the live attenuated measles vaccine (LAV) also provides protection from measles. The level of neutralizing antibody is a good indicator of protection, but the independent roles of MeV-specific antibody and T cells have not been identified. In this study, macaques immunized with LAV through a nebulizer and a mouthpiece developed MeV-specific T-cell responses but not neutralizing antibodies. Upon challenge with wild-type MeV, these animals developed rashes and viremias similar to those in naive animals but cleared viral RNA from blood 25 to 40 days faster. The nebulizer-immunized animals also had more robust MeV-specific CD4(+) and CD8(+) T-cell responses than the naive animals after challenge, characterized by a higher number and better durability of gamma interferon (IFN-γ)-producing cells. Induction of MeV-specific circulating CD4(+) and CD8(+) T cells capable of producing multiple cytokines correlated with clearance of viral RNA in the nebulizer-immunized macaques. These studies demonstrated that MeV-specific T-cell immunity alone did not prevent measles, but T-cell priming enhanced the magnitude, durability, and polyfunctionality of MeV-specific T cells after challenge infection and correlated with more rapid clearance of MeV RNA. IMPORTANCE The components of vaccine-induced immunity necessary for protection from infection and disease have not been clearly identified for most vaccines. Vaccine development usually focuses on induction of antibody, but T-cell-based vaccines are also under development. The live attenuated measles vaccine (LAV) given subcutaneously induces both T cells and neutralizing antibody and provides solid protection from infection. LAV delivered to the upper respiratory tract through a nebulizer and mouthpiece induced a T-cell response but no neutralizing antibody. These T-cell-primed macaques demonstrated no protection from rash or viremia when challenged with wild-type MeV, but viral RNA was cleared more rapidly than in unimmunized animals. Thus, T-cell immunity did not protect from infection or acute disease but facilitated virus clearance during recovery. These studies demonstrate the importance and independent roles of T cells and antibody in protection and recovery from measles.
authors.forename: Wen-Hsuan W
authors.initials: WH
authors.lastname: Lin
authors.forename: Chien-Hsiung
authors.initials: CH
authors.lastname: Pan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: Beth L
authors.initials: BL
authors.lastname: Laube
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D008253:Macaca mulatta; D008457:Measles / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D008458:Measles Vaccine / Q000008:administration & dosage / Q000276:immunology*; D008459:Measles virus / Q000276:immunology* / Q000302:isolation & purification; D012367:RNA, Viral / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D008458:Measles Vaccine; D012367:RNA, Viral; D014613:Vaccines, Attenuated
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