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Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector

Giel-Moloney, M;Esteban, M;Oakes, BH;Vaine, M;Asbach, B;Wagner, R;Mize, GJ;Spies, AG;McElrath, J;Perreau, M;Roger, T;Ives, A;Calandra, T;Weiss, D;Perdiguero, B;Kibler, KV;Jacobs, B;Ding, S;Tomaras, GD;Montefiori, DC;Ferrari, G;Yates, NL;Roederer, M;Kao, S

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.