Evidence for immune-mediated reduction of viral replication in Macaca nemestrina mucosally immunized with inactivated SHIV(89.6).
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.
Ambrose
Zandrea
Z
Department of Pathobiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA.
Thompson
Jannelle
J
Larsen
Kay
K
Kuller
Larene
L
Panicali
Dennis L
DL
Clements
John D
JD
Agy
Michael
M
Montefiori
David C
DC
Hu
Shiu Lok
SL
Bosch
Marnix L
ML
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*
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004279:DNA, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012367:RNA, Viral; D014614:Vaccines, Synthetic