title: Modulation of disease, T cell responses, and measles virus clearance in monkeys vaccinated with H-encoding alphavirus replicon particles.
abstract: Measles remains a major worldwide problem partly because of difficulties with vaccination of young infants. New vaccine strategies need to be safe and to provide sustained protective immunity. We have developed Sindbis virus replicon particles that express the measles virus (MV) hemagglutinin (SIN-H) or fusion (SIN-F) proteins. In mice, SIN-H induced high-titered, dose-dependent, MV-neutralizing antibody after a single vaccination. SIN-F, or SIN-H and SIN-F combined, induced somewhat lower responses. To assess protective efficacy, juvenile macaques were vaccinated with a single dose of 10(6) or 10(8) SIN-H particles and infant macaques with two doses of 10(8) particles. A dose of 10(8) particles induced sustained levels of high-titered, MV-neutralizing antibody and IFN-gamma-producing memory T cells, and most monkeys were protected from rash when challenged with wild-type MV 18 months later. After challenge, there was a biphasic appearance of H- and F-specific IFN-gamma-secreting CD4+ and CD8+ T cells in vaccinated monkeys, with peaks approximately 1 and 3-4 months after challenge. Viremia was cleared within 14 days, but MV RNA was detectable for 4-5 months. These studies suggest that complete clearance of MV after infection is a prolonged, phased, and complex process influenced by prior vaccination.
authors.affiliation: W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Chien-Hsiung
authors.initials: CH
authors.lastname: Pan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Valsamakis
authors.forename: Teresa
authors.initials: T
authors.lastname: Colella
authors.forename: Nitya
authors.initials: N
authors.lastname: Nair
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: Fernando P
authors.initials: FP
authors.lastname: Polack
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Greer
authors.forename: Silvia
authors.initials: S
authors.lastname: Perri
authors.forename: John M
authors.initials: JM
authors.lastname: Polo
authors.forename: Diane E
authors.initials: DE
authors.lastname: Griffin
mesh_terms: D000375:Aging / Q000502:physiology; D000524:Alphavirus / Q000235:genetics* / Q000502:physiology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008251:Macaca / Q000276:immunology / Q000821:virology; D008457:Measles / Q000276:immunology* / Q000821:virology*; D008458:Measles Vaccine / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008459:Measles virus / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014771:Virion / Q000235:genetics / Q000276:immunology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D008458:Measles Vaccine; D012367:RNA, Viral; D007371:Interferon-gamma