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 GilbertAmine Kamen, Xiao Jian Yao, Keith R. Fowke, Eric Arts, Gary Kobinger

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number369
JournalVaccines
Volume12
Issue number4
DOIs
StatePublished - Apr 2024

Keywords

  • DNA vaccine
  • HIV
  • rhesus macaque
  • SHIV
  • VSV vaccine

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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