Sci Rep. 2019 Dec 27; 9(1):20005.

PubMed ID: 31882800

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 SF, Foulds KE, Mayer BT, Bennett C, Gottardo R, Parrington M, Tartaglia J, Phogat S, Pantaleo G, Kleanthous H, Pugachev KV

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.