Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.
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.
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, SF; Foulds, KE; Mayer, BT; Bennett, C; Gottardo, R; Parrington, M; Tartaglia, J; Phogat, S; Pantaleo, G; Kleanthous, H; Pugachev, KV
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