title: Long-term protection in hamsters against human parainfluenza virus type 3 following mucosal or combinations of mucosal and systemic immunizations with chimeric alphavirus-based replicon particles.
abstract: No licensed vaccines are available to protect against parainfluenza virus type 3 (PIV3), a significant health risk for infants. In search of a safe vaccine, we used an alphavirus-based chimeric vector, consisting of Sindbis virus (SIN) structural proteins and Venezuelan equine encephalitis virus (VEE) replicon RNA, expressing the PIV3 hemagglutinin-neuraminidase (HN) glycoprotein (VEE/SIN-HN). We compared different routes of intramuscular (i.m.), intranasal (i.n.), or combined i.n. and i.m. immunizations with VEE/SIN-HN in hamsters. Six months after the final immunization, all hamsters were protected against live PIV3 i.n. challenge in nasal turbinates and lungs. This protection appeared to correlate with antibodies in serum, nasal turbinates and lungs. This is the first report demonstrating mucosal protection against PIV3 for an extended time following immunizations with an RNA replicon delivery system.
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Emeryville, CA 94608, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Greer
authors.forename: F
authors.initials: F
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Goodsell
authors.forename: H S
authors.initials: HS
authors.lastname: Legg
authors.forename: Z
authors.initials: Z
authors.lastname: Tang
authors.forename: J
authors.initials: J
authors.lastname: zur Megede
authors.forename: Y
authors.initials: Y
authors.lastname: Uematsu
authors.forename: J M
authors.initials: JM
authors.lastname: Polo
authors.forename: M
authors.initials: M
authors.lastname: Vajdy
mesh_terms: D000281:Administration, Intranasal; D000524:Alphavirus / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D006224:Cricetinae; D004195:Disease Models, Animal; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology; D006801:Humans; D007114:Immunization; D007273:Injections, Intramuscular; D009092:Mucous Membrane / Q000276:immunology*; D022241:Parainfluenza Vaccines / Q000276:immunology*; D010224:Parainfluenza Virus 3, Human / Q000254:growth & development / Q000276:immunology*; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D012093:Replicon / Q000235:genetics / Q000276:immunology*; D012845:Sindbis Virus / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D022241:Parainfluenza Vaccines; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic