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

Autor: Giel-Moloney M; Sanofi Pasteur, Cambridge, MA, 02139, USA. Maryann.Giel-Moloney@sanofi.com., Esteban M; Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain., Oakes BH; Sanofi Pasteur, Cambridge, MA, 02139, USA., Vaine M; Sanofi Pasteur, Cambridge, MA, 02139, USA., Asbach B; University of Regensburg (UREG), Institute of Medical Microbiology and Hygiene, 93053, Regensburg, Germany., Wagner R; University of Regensburg (UREG), Institute of Medical Microbiology and Hygiene, 93053, Regensburg, Germany.; University Hospital Regensburg, Institute of Clinical Microbiology and Hygiene, 93053, Regensburg, Germany., Mize GJ; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, 98109, USA., Spies AG; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, 98109, USA., McElrath J; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, 98109, USA., Perreau M; Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1011, Lausanne, Switzerland., Roger T; Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, 1011, Lausanne, Switzerland., Ives A; Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, 1011, Lausanne, Switzerland., Calandra T; Infectious Diseases Service, Department of Medicine, Lausanne University Hospital, 1011, Lausanne, Switzerland., Weiss D; Bioqual Inc, Rockville, Maryland, 20850, USA., Perdiguero B; Centro Nacional de Biotecnología (CNB-CSIC), Madrid, Spain., Kibler KV; Arizona State University (ASU), Tucson, AZ, 85745, USA., Jacobs B; Arizona State University (ASU), Tucson, AZ, 85745, USA., Ding S; EuroVacc, Amsterdam, The Netherlands., Tomaras GD; Duke University Medical Center, Durham, North Carolina, 27710, USA., Montefiori DC; Duke University Medical Center, Durham, North Carolina, 27710, USA., Ferrari G; Duke University Medical Center, Durham, North Carolina, 27710, USA., Yates NL; Duke University Medical Center, Durham, North Carolina, 27710, USA., Roederer M; Vaccine Research Center, NIAID, NIH, Bethesda, MD, 20892, USA., Kao SF; Vaccine Research Center, NIAID, NIH, Bethesda, MD, 20892, USA., Foulds KE; Vaccine Research Center, NIAID, NIH, Bethesda, MD, 20892, USA., Mayer BT; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, 98109, USA., Bennett C; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, 98109, USA., Gottardo R; Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, 98109, USA., Parrington M; Sanofi Pasteur, Cambridge, MA, 02139, USA., Tartaglia J; Sanofi Pasteur, Cambridge, MA, 02139, USA., Phogat S; Sanofi Pasteur, Cambridge, MA, 02139, USA., Pantaleo G; Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, 1011, Lausanne, Switzerland., Kleanthous H; Sanofi Pasteur, Cambridge, MA, 02139, USA., Pugachev KV; Sanofi Pasteur, Cambridge, MA, 02139, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Dec 27; Vol. 9 (1), pp. 20005. Date of Electronic Publication: 2019 Dec 27.
DOI: 10.1038/s41598-019-56550-4
Abstrakt: 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.
Databáze: MEDLINE
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