Optimization of an innate immune stimulating adjuvant for an HIV DNA vaccine

Abstract There is a growing consensus that protection against HIV infection will require BOTH antiviral antibody responses as well as polyfunctional CDand CDT cells with potent lytic activityTo stimulate the breadthpotencyand rate of response requiredProfectus Biosciences intends to utilize its platform technologies based on DNA vaccines combined with genetic adjuvantsAs a step in that directiona phaseclinical trialHVTNshowed that electroporation in combination with our ILadjuvant can double the CDand CDT cell response rate in vaccinees over electroporation aloneEven with this successwe recognize that a truly effective HIV vaccine will require a regimen that can consistently provide high magnitudelong lived responses at rates andgtwith as few booster immunizations as possibleWe believe that adjuvants are a key to developing such a vaccineUnder our phase I SBIRswe identified a new class of genetic adjuvants that exploit the RIG I signaling cascades and trigger potent anti viral innate immune responsesThese innate responses integrate with TLR evoked innate responses and DAMPs alarmins to evoke potent anti viral adaptive immune responsesAlso under phase Iwe found that the adjuvants attenuated vaccine antigen expression by negatively impacting the promoterWe have now developed an improved promoter to drive our vaccine antigen and adjuvant expression that is not attenuated by these adjuvantsUnder this phase II SBIRwe intend to identify an optimal combination of DNA adjuvants using a macaque modelUpon completion of phase IIwe expect to have identified a lead adjuvant combination worthy of testing with our HIV vaccine in phase I human trialsProject Narrative The objective of this project is to optimize a novel adjuvant for an HIV DNA vaccineSuch a vaccine adjuvant combination is needed to combat the HIV epidemic