Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV

Hiva Azizi, Jason P. Knapp, Yue Li, Alice Berger, Marc Alexandre Lafrance, Jannie Pedersen, Marc Antoine de la Vega, Trina Racine, Chil Yong Kang, Jamie F.S. Mann, Jimmy D. Dikeakos, Gary Kobinger, Eric J. Arts

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Vesicular stomatitis virus (VSV) remains an attractive platform for a potential HIV-1 vaccine but hurdles remain, such as selection of a highly immunogenic HIV-1 Envelope (Env) with a maximal surface expression on recombinant rVSV particles. An HIV-1 Env chimera with the transmembrane domain (TM) and cytoplasmic tail (CT) of SIVMac239 results in high expression on the approved Ebola vaccine, rVSV-ZEBOV, also harboring the Ebola Virus (EBOV) glycoprotein (GP). Codon-optimized (CO) Env chimeras derived from a subtype A primary isolate (A74) are capable of entering a CD4+/CCR5+ cell line, inhibited by HIV-1 neutralizing antibodies PGT121, VRC01, and the drug, Maraviroc. The immunization of mice with the rVSV-ZEBOV carrying the CO A74 Env chimeras results in anti-Env antibody levels as well as neutralizing antibodies 200-fold higher than with the NL4-3 Env-based construct. The novel, functional, and immunogenic chimeras of CO A74 Env with the SIV_Env-TMCT within the rVSV-ZEBOV vaccine are now being tested in non-human primates.

Original languageEnglish (US)
Article number977
JournalVaccines
Volume11
Issue number5
DOIs
StatePublished - May 2023

Keywords

  • Ebola virus glycoprotein
  • HIV-1 Envelope glycoprotein
  • human immunodeficiency virus type 1 (HIV-1)
  • vesicular stomatitis virus (VSV) vector

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV'. Together they form a unique fingerprint.

Cite this