title: Evidence for immune-mediated reduction of viral replication in Macaca nemestrina mucosally immunized with inactivated SHIV(89.6).
abstract: Although most HIV-1 infections worldwide result from heterosexual transmission, most vaccine candidates have focused on induction of systemic immunity and protection. We hypothesized that combining systemic priming with mucosal boosting would induce mucosal immunity that would protect from intravaginal challenge. Macaques were primed systemically with recombinant vaccinia viruses and boosted mucosally using inactivated SHIV(89.6) plus adjuvant. Other animals received protein boosts with adjuvant alone. Priming and boosting induced antiviral IgG and IgA antibodies. Such antibodies were induced to a lesser degree in animals receiving boosts alone. Anti-SHIV T cell responses were induced only in the prime-boost animals. Immunized animals and controls were challenged intravaginally with SHIV(89.6) and significant reductions in proviral and viral RNA loads were observed in the prime-boost animals. The boost-only animals did not have significant viral load reductions. These data suggest that cellular immunity was required for protection from intravaginal challenge. This immunization regimen provides a promising lead for vaccine development.
authors.affiliation: Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Zandrea
authors.initials: Z
authors.lastname: Ambrose
authors.forename: Jannelle
authors.initials: J
authors.lastname: Thompson
authors.forename: Kay
authors.initials: K
authors.lastname: Larsen
authors.forename: Larene
authors.initials: L
authors.lastname: Kuller
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Panicali
authors.forename: John D
authors.initials: JD
authors.lastname: Clements
authors.forename: Michael
authors.initials: M
authors.lastname: Agy
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Shiu Lok
authors.initials: SL
authors.lastname: Hu
authors.forename: Marnix L
authors.initials: ML
authors.lastname: Bosch
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D007114:Immunization / Q000379:methods; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D017958:Lentiviruses, Primate / Q000276:immunology*; D008254:Macaca nemestrina; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012367:RNA, Viral; D014614:Vaccines, Synthetic