CD40L adjuvanted clade C DNA and MVA HIV vaccines

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DESCRIPTION (provided by applicant): Development of an effective vaccine against HIV-1 has been an elusive goal for the past three decades. As a result it has been a major challenge to stem the tide of the epidemic caused by this virus globally. The results of the RV44 efficacy trial in Thailand have spurred a new level of excitement for the development of HIV vaccine and strongly support the development of vaccination approaches that enhance the titer and functional quality of anti-HIV Env antibody that may significantly enhance protection against HIV. The overall goal of this program is to develop novel vaccination approaches that not only enhance the magnitude but also enhance the functional quality of anti-HIV cellular and humoral immunity. Specifically, we propose to combine two new vaccination approaches developed recently at Emory University that showed great promise in rhesus macaques. The first approach uses CD40L, a co-stimulatory molecule for dendritic cells (DC) and B cells, expressed on the surface of HIV VLPs as a genetic adjuvant for enhancing the magnitude and functional quality of HIV-specific cellular and humoral immunity leading to enhanced protection from acquisition of SIV infection. The second approach uses a new MVA that lacks 4 immune modulatory genes (MVAA4) as a vaccine vector that showed a significant increase in the magnitude of HIV-specific cellular and humoral immunity in rhesus macaques. In this program, we hope to combine these two new complementary approaches to develop a novel vaccination strategy against HIV. This program will be a collaborative effort between scientists at the Emory University (Drs. Amara, Mulligan, Derdeyn, and Velu), NIH (Dr. Moss), International AIDS Vaccine Initiative (lAVI; Dr. Dean), Walter Reed Army Institute of Research (WRAIR; Dr. Michael), Louisiana State University (LSU; Dr. Kozlowski) and CDC (Dr. Garber). This Program has 3 projects and two cores. The proposed program builds upon the enormous experience with our DNA and MVA vaccines in the preclinical and clinical settings and strong preliminary data with the new vaccines in the preclinical model. Successful completion of the program will result in the clinical development of two new vaccine products and a novel HIV vaccine.