TY - JOUR
T1 - Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV
AU - Azizi, Hiva
AU - Knapp, Jason P.
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.
N1 - Funding Information:
This research was funded by the National Institutes of Health (grant number AI49170), the Canadian Institutes of Health Research (grant number 421693), and the Canada Research Chair grants to E.J.A. and K.P. This research was performed in the ImPaKT Centre, funded by the Canada Foundation for Innovation (grant number 42789). The funders played no role in the study design, data collection, the analysis and interpretation of data, or the writing of this manuscript.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - Ebola virus glycoprotein
KW - HIV-1 Envelope glycoprotein
KW - human immunodeficiency virus type 1 (HIV-1)
KW - vesicular stomatitis virus (VSV) vector
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U2 - 10.3390/vaccines11050977
DO - 10.3390/vaccines11050977
M3 - Article
C2 - 37243081
AN - SCOPUS:85160310324
SN - 2076-393X
VL - 11
JO - Vaccines
JF - Vaccines
IS - 5
M1 - 977
ER -