440. Extreme Polyvalency Induces Potent Cross-Clade Cellular and Humoral Responses in Rabbits and Non-Human Primates

There is a pressing need to determine possible unique vaccine combinations of Envs which induce enhanced breadth and functional antibody responses. Due to the ease of manufacturing and formulation, we sought to determine if increased breadth within a vaccine correlates with robust and broad responses. We have developed over 40 different DNA plasmids expressing consensus as well as primary Envs. We have shown that each of these plasmids are able to induce both cellular and humoral responses in mice. Different combinations of Envs were testing in rabbits to further characterize the humoral responses and explore neutralization. Rabbits immunized with clusters of clade A transmitter founder (TF) gp160 DNA induced cross-clade binding titers with limited neutralization. Including TF Envs from different clades, increased binding titers as well as neutralization breadth and potency. Formulating the gp160s to be administered to the same site induced quicker seroconversion than delivering the Envs at separate sites. The most potent combination was moved forward into NHPs, which were immunized with clusters of gp160 DNAs (14 different Envs in total) at weeks 0, 4, 8, 12 and boosted at weeks 48 and 85. The vaccine induced cross-clade cellular and humoral responses after two immunizations. These responses increased after each immunization and were maintained into memory. In addition to binding, vaccination also induced tier 1 neutralization. Boosting at week 48 and 85 further increased both responses. We show that DNA plasmids encoding consensus and TF Envs are expressed and induce a potent immune responses. We observed for the first time that exposure of the immune system to multiple Envs at one time can dramatically change the immune phenotype by inducing broader breadth of response which has significant implications for HIV vaccine development.