Improved Venezuelan equine encephalitis virus vaccines

We hypothesize that the application of the broad-spectrum immune-stimulatory and -modulatory HyperAcute alphaGal Adjuvant Technology will enhance the potency and effectiveness of VEEV vaccine candidates. To complement the exciting preclinical and clinical results obtained with alphaGal-modified anti-cancer vaccines, and preclinical studies with both Ebolavirus and Influenza virus, we will apply the alphaGal Adjuvant Technology to improve the potency of antiviral vaccine candidates for VEEV. Initially, we will focus on the improvement of different vaccine candidates against VEEV as a proof of concept of the broad applicability of the alphaGal Adjuvant Technology. We will generate and compare the immunogenicity and efficacy of several alphaGal-modified VEEV vaccine candidates. For that we will: (i) Generate alphaGal-modified vaccines, (ii) Develop the assays required for potency, purity, identity and quality, (iii) determine the immunogenicity of alphaGal-modified vaccines in a mouse model, (iv) identify the most potent vaccine candidates by lethal challenge experiments in a mouse model (under BSL-4 conditions), (v) develop and validate assays to support vaccine cGMP manufacturing and cGMP lot release testing and (vi) perform efficacy studies with most potent vaccine candidates by lethal challenge experiments in a NHP model.