Enhancing protective antibody responses for a DNA MVA HIV vaccine

DESCRIPTION provided by applicant The proposed work addresses a pivotal study for decisions on the form of the GeoVax Clade B HIV vaccine GOVX B to be taken into efficacy trials GOVX B is a DNA MVA vaccine that expresses virus like particles VLPs displaying trimeric membrane bound Env It has been under development for more than years during which time it has demonstrated unique properties and shown considerable promise in both preclinical and clinical studies Phase I of this SBIR tested the ability of monovalent gp and gp boosts to enhance the immunogenicity of GOVX B This Phase II proposal builds on the Phase I results to test a bivalent gp boost and to extend preclinical testing to include a challenge study The Clade B epidemic continues to be a major public health problem in the Americas Although the US epidemic does not receive the publicity received by the epidemic in Africa and should theoretically be able to be controlled with drugs HIV remains a major US health problem Costs of HIV care and treatment rose from $ billion in to just under $ billion in a high and increasing burden for taxpayers Kaiser Foundation Fact Sheet June Financial costs alone demonstrate the critical need for a vaccine Social costs of each HIV infection are also large including patient time lost productivity and physical and emotional distress to patients and their families Specific Aim To conduct a preclinical trial GV M testing a bivalent protein boost for GOVX B The proposed bivalent boost consists of a transmitted founder gp B delta a CD induced form of Bal gp FLSC The primary goals of this specific aim are to oversee the conduct of the trial and to collect safet data for a trial that will include the D D domains of CD in an immunogen Specific Aim To obtain immunogenicity data for the bivalent protein boost The primary goal of this Specific Aim is to test the effect of the bivalent boost on the titer isotype specificity breadth and functio of antibody Ab to Env Particular emphasis will be placed on Ab for the V V V and C regions of gp and the ADCC activity of the elicited Ab all of which were associated with reduced risk in the partially successful RV trial Specific Aim To determine the effect of the bivalent B delta FLSC boost on the ability to protect against serial rectal challenges with SHIV P The primary goals of this Specific Aim are to determine whether the bivalent protein boost increases protection against acquisition and to determine which Ab and T cell responses decrease acquisition and how these responses relate to those that decreased the risk of infection in the RV trial PUBLIC HEALTH RELEVANCE This project addresses the unmet need for an HIV vaccine for the clade B epidemic in the United States Central and South America It continues the development of GOVX B a vaccine that consists of priming with a recombinant DNA and boosting with a recombinant live virus MVA and tests the ability of a bivalent protein boost to enhance the efficacy of GOVX B The studies are conducted in the rhesus macaque model and represent a collaboration of scientists at GeoVax the Duke University Human Vaccine Institute and Profectus Biosciences Inc