Intranasal Delivery of HIV/SIV Antigens with NE/AS01B Adjuvants Enhances Cellular Immunity and Reduces Viral Loads in SHIV-Challenged Macaques

The primary route of HIV transmission is across mucosal tissues; therefore, developing a protective mucosal vaccine is a top priority. In a pilot study, using a macaque model, we delivered HIV gp140 envelope glycoprotein and SIVmac239 P55 Gag and Nef antigens using heterologous prime/boost via the intranasal route with a soybean oil-based nanoemulsion (NE) adjuvant and through the intramuscular route with the AS01B adjuvant system to generate enhanced cell-mediated immunity. We used a NE adjuvant to promote gut-homing cell-mediated immunity and the AS01B system to enhance humoral immune responses. Following intrarectal challenge with SHIV 4MTF.tHy, vaccinated macaques acquired the virus but experienced lower viral loads in plasma (P=0.003) and CSF (P=0.001), and potent polyfunctional gag-specific (CD107a+, IFNγ, TNFα+) responses across diverse lymph nodes. Significant antibody-dependent complement deposition (ADCD) and antibody-dependent cellular phagocytosis (ADCP) responses were induced, and gut-microbiome crosstalk could be modulated and showing reduced SHIV-dysbiosis. Notably, vaccination preserved mucosal all-trans retinoic acid levels (atRA) (p<0.05). However, no significant differences were observed for antibody responses between vaccinated and unvaccinated macaques. In summary, the induced gut-homing properties by the NE adjuvant are effective at generating cell-mediated immunity and reducing viral set points and warrant further investigations as a mucosal adjuvant in HIV vaccine design.