Enhancement of mucosal antibody responses to HIV vaccine

DESCRIPTION (provided by applicant): Since 1981, when HIV was first recognized as a serious and deadly disease, the number of infected people has risen to nearly 60 million. There are approximately 14,000 new HIV infections per day, and the WHO predicts th at HIV poses the greatest threat to global health in the coming years. Having already claimed more than 20 million lives, HIV/AIDS still remains a largely unmet medical need. The severe nature and poor prognosis associated with this disease, together with high global prevalence and lack of simple and effective treatment, have driven demand for prophylactic vaccines against HIV. As it is the case with other infectious diseases, a safe, effective and available preventive vaccine will ultimately be the preferr ed method in our fight to end the HIV pandemic. Although developing an effective HIV vaccine remains one of the highest priorities, it also presents formidable scientific challenges to researchers. Currently, there are no HIV vaccines available. Zetra Biol ogicals, LLC has exclusively licensed novel platform technology from Emory University for vaccine discovery, development and production. Recent data, produced by using our patent protected and patent pending technology, demonstrated that chimeric virus-lik e particle vaccine candidates elicit strong innate and acquired immune responses. In pre-clinical studies with an early vaccine candidate we have demonstrated a broad antibody and T-cell responses against HIV-1. In Phase I of this project we are planning t o leverage our expertise in creating novel HIV vaccine candidates and capabilities of our platform chimeric virus-like particle technology to further develop new HIV vaccine candidates. Our objective is to create chimeric VLPs with membrane-anchored toll-l ike receptor ligands as a novel HIV-1 vaccine candidate with a goal to elicit broadly anti-HIV neutralizing antibodies and strong mucosal immune responses. The specific aims of the Phase I project are: 1) To produce chimeric virus-like particles (cVLPs) in corporating HIV glycoproteins and membrane-anchored adjuvant molecules; 2) To evaluate the immunogenicity of novel HIV chimeric VLPs in comparison to standard VLPs containing Env and Gag proteins. PUBLIC HEALTH RELEVANCE: More than 60 million people have b een infected with the HIV virus, and AIDS has taken the lives of more than 20 million adults and children. With 14,000 new HIV infections every day, HIV continues to spread. Our recent studies on HIV-1 and SIV demonstrated that vaccines produced by using o ur novel platform technology can offer an alternative strategy for development of an effective, safe, and affordable HIV vaccine. In the proposed project, we will demonstrate that novel chimeric virus-like particles with an incorporated toll-like receptor ligand will induce and enhance immune responses against the HIV-1 virus.