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. Objective: To determine if Invaplex can adjuvant nasal DNA- or protein-based vaccines in nonhuman primates. Methods. Three groups of female rhesus macaques were nasally immunized on weeks 0, 4, and 8 with SIV gp130 protein and SHIV89.6 DNA. In Groups 2 and 3, the DNA/protein formulation was co-administered with 0.25mg and 0.5mg Invaplex, respectively. Five months later, all animals were nasally boosted with adenovirus vectors expressing SIV antigens (Ad-SIV). ELISA was used to quantitate SIV antibodies in serum and secretions. Intracellular cytokine staining was used to monitor T cell responses. Results: When compared to Group 1, animals in Group 3 demonstrated significantly greater SIV env-specific IgG in serum and IgA in secretions after the 3rd immunization. Systemic IgG and mucosal IgA to DNA-encoded antigens were also enhanced in Group 3. On wk12, Group 3 also demonstrated significantly greater frequencies of circulating SIV env-specific T cells secreting IFN-g. Group 2 exhibited intermediate responses that did not differ significantly from Group 1 or 3. Nasal boosting with Ad-SIV elevated SIV-specific antibodies in Group 3 to a significantly greater extent than Group 1. All groups had similar percentages of SIV env- and gag-specific T cells secreting IFN-g- and TNF-a-secreting in blood. Conclusions: Invaplex can adjuvant antibody and T cell responses to nasal protein immunogens in nonhuman primates. Invaplex can also enhance antibody generated after nasal DNA vaccination. Invaplex could potentially be used as an adjuvant for both nasal DNA and protein vaccines in humans.