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

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) an...

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Bibliographic Details
Published in:Vaccines (Basel) 2023-05, Vol.11 (5), p.977
Main Authors: Azizi, Hiva, Knapp, Jason P, Li, Yue, Berger, Alice, Lafrance, Marc-Alexandre, Pedersen, Jannie, de la Vega, Marc-Antoine, Racine, Trina, Kang, Chil-Yong, Mann, Jamie F S, Dikeakos, Jimmy D, Kobinger, Gary, Arts, Eric J
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
AIDS vaccines
Antibodies
Antigens
CCR5 protein
CD4 antigen
Chimeras
Cloning
Complications and side effects
Ebola virus
Ebola virus glycoprotein
Ebolavirus
Genes
Genomes
Glycoproteins
Highly active antiretroviral therapy
HIV
HIV (Viruses)
HIV-1 Envelope glycoprotein
Human immunodeficiency virus
human immunodeficiency virus type 1 (HIV-1)
Immunization
Immunogenicity
Infections
Localization
Neutralizing
Patient outcomes
Prevention
Proteins
Reagents
Stomatitis
Vaccines
vesicular stomatitis virus (VSV) vector
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Summary: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.
ISSN:2076-393X
2076-393X
DOI:10.3390/vaccines11050977