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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/5/977 |
| _version_ | 1797598159329820672 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Hiva Azizi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T03:15:24Z |
| format | Article |
| id | doaj.art-5fb10575b302437c965355e5448185ca |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T03:15:24Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-5fb10575b302437c965355e5448185ca2023-11-18T03:36:34ZengMDPI AGVaccines2076-393X2023-05-0111597710.3390/vaccines11050977Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOVHiva Azizi0Jason P. Knapp1Yue Li2Alice Berger3Marc-Alexandre Lafrance4Jannie Pedersen5Marc-Antoine de la Vega6Trina Racine7Chil-Yong Kang8Jamie F. S. Mann9Jimmy D. Dikeakos10Gary Kobinger11Eric J. Arts12Département de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, CanadaDepartment of Microbiology and Immunology, Western University, London, ON N6A 3K7, CanadaDepartment of Microbiology and Immunology, Western University, London, ON N6A 3K7, CanadaDépartement de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, CanadaDépartement de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, CanadaDépartement de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, CanadaDépartement de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, CanadaDépartement de Microbiologie-Infectiologie et Immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, CanadaDepartment of Microbiology and Immunology, Western University, London, ON N6A 3K7, CanadaBristol Veterinary School, University of Bristol, Langford House, Langford, BS40 5DU Bristol, UKDepartment of Microbiology and Immunology, Western University, London, ON N6A 3K7, CanadaGalveston National Laboratory, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, Western University, London, ON N6A 3K7, CanadaVesicular 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.https://www.mdpi.com/2076-393X/11/5/977human immunodeficiency virus type 1 (HIV-1)vesicular stomatitis virus (VSV) vectorHIV-1 Envelope glycoproteinEbola virus glycoprotein |
| spellingShingle | 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 Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV Vaccines human immunodeficiency virus type 1 (HIV-1) vesicular stomatitis virus (VSV) vector HIV-1 Envelope glycoprotein Ebola virus glycoprotein |
| title | Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV |
| title_full | Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV |
| title_fullStr | Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV |
| title_full_unstemmed | Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV |
| title_short | Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV |
| title_sort | optimal expression function and immunogenicity of an hiv 1 vaccine derived from the approved ebola vaccine rvsv zebov |
| topic | human immunodeficiency virus type 1 (HIV-1) vesicular stomatitis virus (VSV) vector HIV-1 Envelope glycoprotein Ebola virus glycoprotein |
| url | https://www.mdpi.com/2076-393X/11/5/977 |
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