Prime/boost immunizations using DNA priming and recombinant MVA boosters have proved to raise much higher levels of T cells than either DNA or MVA immunizations alone. The goals of this Program Project are to evaluate the cross clade activity of DNA /MVA protocols for immunodeficiency virus vaccines. Can worldwide vaccination be accomplished with a single DNA/MVA immunogen, or will a mixture of DNA/MVA immunogens, or geographically targeted clade-specific immunogens, be necessary? The charges for Project 2 are to perform the preclinical testing that will determine which DNAs or formulated DNAs will be used for priming MVA boosters in human trials, and to provide preclinical data to support IND applications for human trials. One major goal for Project 2 is to determine in preclinical models how DNA/MVA immunogens from two different clades affect the height and breadth of T-cell responses compared to those raised by single clade immunogens. A second major goal is to identify conditions that will allow the amount of DNA needed for priming MVA boosters to be reduced by ten-fold. Project 2 will be accomplished by a team of Emory investigators. Dr. Ahmed will be responsible for screening novel DNAs and formulated DNAs in mouse models for effects on the height and breadth of the memory T cell response. Dr. Robinson will be responsible for GLP studies in macaques testing the ability of selected immunogens, both singly and in combination, to raise memory T-cell responses. Studies will be done with clade B immunogens that represent the HIV-1 epidemic in North America and with clade AG immunogens that match the predominant infection at the CDC test site in Abidjan, Cote d'lvoire.
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