Impact of Recombinant VSV-HIV Prime, DNA-Boost Vaccine Candidates on Immunogenicity and Viremia on SHIV-Infected Rhesus Macaques
Alice Berger,
Jannie Pedersen,
Monika M. Kowatsch,
Florine Scholte,
Marc-Alexandre Lafrance,
Hiva Azizi,
Yue Li,
Alejandro Gomez,
Matthew Wade,
Hugues Fausther-Bovendo,
Marc-Antoine de La Vega,
Joseph Jelinski,
George Babuadze,
Marie-Edith Nepveu-Traversy,
Claude Lamarre,
Trina Racine,
Chil-Yong Kang,
Bruno Gaillet,
Alain Garnier,
Rénald Gilbert,
Amine Kamen,
Xiao-Jian Yao,
Keith R. Fowke,
Eric Arts,
Gary Kobinger
Affiliations
Alice Berger
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Jannie Pedersen
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Monika M. Kowatsch
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Florine Scholte
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Marc-Alexandre Lafrance
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Hiva Azizi
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Yue Li
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 3K7, Canada
Alejandro Gomez
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Matthew Wade
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Hugues Fausther-Bovendo
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Marc-Antoine de La Vega
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Joseph Jelinski
Galveston National Laboratory, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
George Babuadze
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Marie-Edith Nepveu-Traversy
Global Urgent and Advanced Research and Development, Batiscan, QC G0X 1A0, Canada
Claude Lamarre
Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Unversité Laval, Quebec, QC G1V 0A6, Canada
Trina Racine
Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, QC G1E 6W2, Canada
Chil-Yong Kang
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 3K7, Canada
Bruno Gaillet
Department of Chemical Engineering, Faculty of Science and Engineering, Laval University, Quebec, QC G1V 0A6, Canada
Alain Garnier
Department of Chemical Engineering, Faculty of Science and Engineering, Laval University, Quebec, QC G1V 0A6, Canada
Rénald Gilbert
Department of Production Platforms and Analytics, Human Health Therapeutics Research Center, National Research Council, Montreal, QC H4P 2R2, Canada
Amine Kamen
Department of Bioengineering, McGill University, Montreal, QC H3A 0G4, Canada
Xiao-Jian Yao
Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, QC G1E 6W2, Canada
Keith R. Fowke
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB R3T 2N2, Canada
Eric Arts
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 3K7, Canada
Gary Kobinger
Galveston National Laboratory, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Currently, no effective vaccine to prevent human immunodeficiency virus (HIV) infection is available, and various platforms are being examined. The vesicular stomatitis virus (VSV) vaccine vehicle can induce robust humoral and cell-mediated immune responses, making it a suitable candidate for the development of an HIV vaccine. Here, we analyze the protective immunological impacts of recombinant VSV vaccine vectors that express chimeric HIV Envelope proteins (Env) in rhesus macaques. To improve the immunogenicity of these VSV-HIV Env vaccine candidates, we generated chimeric Envs containing the transmembrane and cytoplasmic tail of the simian immunodeficiency virus (SIV), which increases surface Env on the particle. Additionally, the Ebola virus glycoprotein was added to the VSV-HIV vaccine particles to divert tropism from CD4 T cells and enhance their replications both in vitro and in vivo. Animals were boosted with DNA constructs that encoded matching antigens. Vaccinated animals developed non-neutralizing antibody responses against both the HIV Env and the Ebola virus glycoprotein (EBOV GP) as well as systemic memory T-cell activation. However, these responses were not associated with observable protection against simian-HIV (SHIV) infection following repeated high-dose intra-rectal SHIV SF162p3 challenges.
