AN ADENOVIRUS SIMIAN IMMUNODEFICIENCY VIRUS ENV VACCINE ELICITS HUMORAL, CELLULAR, AND MUCOSAL IMMUNE-RESPONSES IN RHESUS MACAQUES AND DECREASES VIRAL BURDEN FOLLOWING VAGINAL CHALLENGE

Six female rhesus macaques were immunized orally and intranasally at 0 weeks and intratracheally at 12 weeks with an adenovirus type 5 host range mutant (Ad5hr)-simian immunodeficiency virus SIVsm env recombina nt and at 24 and 36 weeks with native SIV(mac251)gp120 in Syntex adjuv ant. Four macaques received the Ad5hr vector and adjuvant alone; two a dditional controls were naive. In vivo replication of the Ad5hr wild-t ype and recombinant vectors occurred with detection of Ad5 DNA in stoo l samples and/or nasal secretions in all macaques and increases in Ad5 neutralizing antibody in 9 of 10 macaques following Ad administration s. SIV-specific neutralizing antibodies appeared after the second reco mbinant immunization and rose to titers > 10,000 following the second subunit boost. Immunoglobulin G (IgG) and IgA antibodies able to bind gp120 developed in nasal and rectal secretions, and SIV-specific IgGs were also observed in vaginal secretions and saliva. T-cell proliferat ive responses to SIV gp140 and T-helper epitopes were sporadically det ected in all immunized macaques. Following vaginal challenge with SIVm ac251, transient or persistent infection resulted in both immunized an d control monkeys. The mean viral burden in persistently infected immu nized macaques was significantly decreased in the primary infection pe riod compared to that of control macaques. These results establish in vivo use of the Ad5hr vector, which overcomes the host range restricti on of human Ads for rhesus macaques, thereby providing a new model for evaluation of Ad-based vaccines. In addition, they show that a vaccin e regimen using the Ad5hr-SIV env recombinant and gp120 subunit induce s strong humoral, cellular, and mucosal immunity in rhesus macaques. T he reduced viral burden achieved solely with an env-based vaccine supp orts further development of Ad-based vaccines comprising additional vi ral components for immune therapy and AIDS vaccine development.