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

doi:10.3390/vaccines11050977

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

Microbiology And Immunology

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Article number	977
Journal	Vaccines
Volume	11
Issue number	5
DOIs	https://doi.org/10.3390/vaccines11050977
State	Published - 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)

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10.3390/vaccines11050977

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Azizi, H., Knapp, J. P., Li, Y., Berger, A., Lafrance, M. A., Pedersen, J., de la Vega, M. A., Racine, T., Kang, C. Y., Mann, J. F. S., Dikeakos, J. D., Kobinger, G., & Arts, E. J. (2023). Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV. Vaccines, 11(5), Article 977. https://doi.org/10.3390/vaccines11050977

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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.",

keywords = "Ebola virus glycoprotein, HIV-1 Envelope glycoprotein, human immunodeficiency virus type 1 (HIV-1), vesicular stomatitis virus (VSV) vector",

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

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AU - Li, Yue

AU - Berger, Alice

AU - Lafrance, Marc Alexandre

AU - Pedersen, Jannie

AU - de la Vega, Marc Antoine

AU - Racine, Trina

AU - Kang, Chil Yong

AU - Mann, Jamie F.S.

AU - Dikeakos, Jimmy D.

AU - Kobinger, Gary

AU - Arts, Eric J.

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KW - HIV-1 Envelope glycoprotein

KW - human immunodeficiency virus type 1 (HIV-1)

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

Abstract

Keywords

ASJC Scopus subject areas

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