Scientific reports · 2019
Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.
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Giel-Moloney M, Esteban M, Oakes B H, Vaine M, Asbach B, Wagner R, Mize G J, Spies A G, McElrath J, Perreau M, Roger T, Ives A, Calandra T, Weiss D, Perdiguero B, Kibler K V, Jacobs B, Ding S, Tomaras G D, Montefiori D C, Ferrari G, Yates N L, Roederer M, Kao S F, Foulds K E, Mayer B T, Bennett C, Gottardo R, Parrington M, Tartaglia J, Phogat S, Pantaleo G, Kleanthous H, Pugachev K V
Аннотация
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.