A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease
Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the <i>Filoviridae</i> family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/7/1004 |
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| author | Wenjun Zhu Guodong Liu Wenguang Cao Shihua He Anders Leung Ute Ströher Michael J. Fairchild Rick Nichols Joseph Crowell Joan Fusco Logan Banadyga |
| author_facet | Wenjun Zhu Guodong Liu Wenguang Cao Shihua He Anders Leung Ute Ströher Michael J. Fairchild Rick Nichols Joseph Crowell Joan Fusco Logan Banadyga |
| author_sort | Wenjun Zhu |
| collection | DOAJ |
| description | Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the <i>Filoviridae</i> family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Our results demonstrated that a single dose (2 × 10<sup>6</sup> PFU) of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Moreover, protection was robust, with as little as 200 PFU of vaccine conferring significant protection. Not only does this study highlight the potential predictive value of the guinea pig model in the evaluation of MARV countermeasures, but it also demonstrates consistent and reproducible protection afforded by a clonal vaccine candidate. Indeed, this study identifies PHV01 as a suitable vaccine candidate for advanced development. |
| first_indexed | 2024-03-09T12:53:55Z |
| format | Article |
| id | doaj.art-754c6112c51146dcbd11087858918e5e |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T12:53:55Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-754c6112c51146dcbd11087858918e5e2023-11-30T22:02:23ZengMDPI AGVaccines2076-393X2022-06-01107100410.3390/vaccines10071004A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus DiseaseWenjun Zhu0Guodong Liu1Wenguang Cao2Shihua He3Anders Leung4Ute Ströher5Michael J. Fairchild6Rick Nichols7Joseph Crowell8Joan Fusco9Logan Banadyga10Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaSpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaSpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaSpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaSpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaSpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaSpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaPublic Health Vaccines, Cambridge, MA 02142, USAPublic Health Vaccines, Cambridge, MA 02142, USAPublic Health Vaccines, Cambridge, MA 02142, USASpecial Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB R3E 3R2, CanadaMarburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the <i>Filoviridae</i> family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Our results demonstrated that a single dose (2 × 10<sup>6</sup> PFU) of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Moreover, protection was robust, with as little as 200 PFU of vaccine conferring significant protection. Not only does this study highlight the potential predictive value of the guinea pig model in the evaluation of MARV countermeasures, but it also demonstrates consistent and reproducible protection afforded by a clonal vaccine candidate. Indeed, this study identifies PHV01 as a suitable vaccine candidate for advanced development.https://www.mdpi.com/2076-393X/10/7/1004Marburg virusVSV-MARVvesicular stomatitis virusvaccinefilovirus |
| spellingShingle | Wenjun Zhu Guodong Liu Wenguang Cao Shihua He Anders Leung Ute Ströher Michael J. Fairchild Rick Nichols Joseph Crowell Joan Fusco Logan Banadyga A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease Vaccines Marburg virus VSV-MARV vesicular stomatitis virus vaccine filovirus |
| title | A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease |
| title_full | A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease |
| title_fullStr | A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease |
| title_full_unstemmed | A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease |
| title_short | A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease |
| title_sort | cloned recombinant vesicular stomatitis virus vectored marburg vaccine phv01 protects guinea pigs from lethal marburg virus disease |
| topic | Marburg virus VSV-MARV vesicular stomatitis virus vaccine filovirus |
| url | https://www.mdpi.com/2076-393X/10/7/1004 |
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