@article{990f3e06fa764da3badd88cde9d8a92c,
title = "Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector",
abstract = "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.",
author = "M. Giel-Moloney and M. Esteban and Oakes, {B. H.} and M. Vaine and B. Asbach and R. Wagner and Mize, {G. J.} and Spies, {A. G.} and J. McElrath and M. Perreau and T. Roger and A. Ives and T. Calandra and D. Weiss and B. Perdiguero and Kibler, {K. V.} and B. Jacobs and S. Ding and Tomaras, {G. D.} and Montefiori, {D. C.} and G. Ferrari and Yates, {N. L.} and M. Roederer and Kao, {S. F.} and Foulds, {K. E.} and Mayer, {B. T.} and C. Bennett and R. Gottardo and M. Parrington and J. Tartaglia and S. Phogat and G. Pantaleo and H. Kleanthous and Pugachev, {K. V.}",
note = "Funding Information: The study was funded by the Bill & Melinda Gates Foundation (project nr OPP1040705) and we thank Dr. Pervin Amklesaria and Dr. Nina Russell (Gates Foundation) for their guidance of this study. We thank the Poxvirus T-cell Vaccine Discovery Consortium funded by the Bill & Melinda Gates Foundation (OPP38599) for the development and provision of NYVAC and DNA vectors; support for the ICS and antibody immune monitoring assays was provided by the Vaccine Immune Monitoring Centers (OPP1032325 & OPP1032144), and support for the statistical analysis from the Vaccine Immunology Statistical Center (OPP1032317), all part of the Collaboration for AIDS Vaccine Discovery. We thank Hongmei Gao and Kelli Greene (Duke University) for CAVIMC program management, Eva Chung (Fred Hutchinson Cancer Research Center) for VISC program management, Lindsey Galmin (ABL Inc) for NHP study management, and Dora Dong, William Fulp, and Alicia Sato (Fred Hutchinson Cancer Research Center) for their contributions to the data analysis. We thank Dr. Stanley A. Plotkin, Dr. Rafi Ahmed, Dr. Andrew J McMichael, and Dr. Thomas P. Monath (Scientific Advisory Board Members for the study) for their guidance, expertise, and insightful discussions. RepliVax is currently a registered trademark of the Board of Regents of the University of Texas System.",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41598-019-56550-4",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}