VACCINE USING HIV/SIV ENV, GAG, NEF & TAT ADENOVIRUS WITH PROTEIN BOOSTING

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We evaluated the immunogenicity of replication-competent Ad5 host range mutant recombinants (Ad5hr). Efficacy against intravenous SHIV89.6P challenge was tested. Rhesus macaques (8 per group) were primed intranasally (wk 0) and intratracheally (wk 12) with Ad5hr encoding HIVtat (group I), HIVtat + HIV89.6Penv (group II), or HIVtat + HIV89.6Penv + SIV239gag + SIV239nef (group III). Protein subunit boosts (wks 24 and 36), given according to the Ad prime, consisted of HIV Tat (in alum, SC), and HIV89.6pgp140 and SIV239 Nef , both given in MPL-SE, IM. Control animals received Ad5hr-'E3 and adjuvant only. Macaques were challenged (wk 50) with 30 MID50 SHIV89.6P. Tat-specific IFN- ' -secreting cells measured by ELISPOT were low and sporadic over the course of immunization. The number of responders was similar in the 3 vaccination groups (7/8, 6/8, and 6/8 macaques in groups I-III, respectively). Tat-specific proliferative responses were also sporadic and less frequent, with a similar response rate among groups (3/8, 4/8, and 4/8 responders in groups I-III, respectively). Potent cellular immune responses to Env peptides were seen in group II (tat/env) and III (tat/env/gag/nef). In Group III ELISPOT responses were modest to Gag and negligible to Nef. All macaques in groups II and III exhibited proliferative responses to inactivated SHIV89.6P, and in group III, 4/8 and 7/8 responded to p27 and Nef, respectively. All macaques developed binding antibodies to their respective protein boosters. Anti-Tat titers were similar in the 3 groups, and comparable anti-Env titers were exhibited in groups II and III. All macaques in group III mounted a strong antibody response to Nef