A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1
HSV-1 disease is a significant public health burden causing orofacial, genital, cornea, and brain infection. We previously reported that a trivalent HSV-2 gC2, gD2, gE2 nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccine provides excellent protection against vaginal HSV-1 infection in mice. He...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/7/1483 |
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| author | Kevin P. Egan Sita Awasthi Giulia Tebaldi Lauren M. Hook Alexis M. Naughton Bernard T. Fowler Mitchell Beattie Mohamad-Gabriel Alameh Drew Weissman Gary H. Cohen Harvey M. Friedman |
| author_facet | Kevin P. Egan Sita Awasthi Giulia Tebaldi Lauren M. Hook Alexis M. Naughton Bernard T. Fowler Mitchell Beattie Mohamad-Gabriel Alameh Drew Weissman Gary H. Cohen Harvey M. Friedman |
| author_sort | Kevin P. Egan |
| collection | DOAJ |
| description | HSV-1 disease is a significant public health burden causing orofacial, genital, cornea, and brain infection. We previously reported that a trivalent HSV-2 gC2, gD2, gE2 nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccine provides excellent protection against vaginal HSV-1 infection in mice. Here, we evaluated whether this HSV-2 gC2, gD2, gE2 vaccine is as effective as a similar HSV-1 mRNA LNP vaccine containing gC1, gD1, and gE1 in the murine lip and genital infection models. Mice were immunized twice with a total mRNA dose of 1 or 10 µg. The two vaccines produced comparable HSV-1 neutralizing antibody titers, and surprisingly, the HSV-2 vaccine stimulated more potent CD8<sup>+</sup> T-cell responses to gE1 peptides than the HSV-1 vaccine. Both vaccines provided complete protection from clinical disease in the lip model, while in the genital model, both vaccines prevented death and genital disease, but the HSV-1 vaccine reduced day two vaginal titers slightly better at the 1 µg dose. Both vaccines prevented HSV-1 DNA from reaching the trigeminal or dorsal root ganglia to a similar extent. We conclude that the trivalent HSV-2 mRNA vaccine provides outstanding protection against HSV-1 challenge at two sites and may serve as a universal prophylactic vaccine for HSV-1 and HSV-2. |
| first_indexed | 2024-03-11T00:34:07Z |
| format | Article |
| id | doaj.art-4ef81b6da24b4b0e90b0bd78a21e8ba3 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T00:34:07Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-4ef81b6da24b4b0e90b0bd78a21e8ba32023-11-18T21:44:19ZengMDPI AGViruses1999-49152023-06-01157148310.3390/v15071483A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1Kevin P. Egan0Sita Awasthi1Giulia Tebaldi2Lauren M. Hook3Alexis M. Naughton4Bernard T. Fowler5Mitchell Beattie6Mohamad-Gabriel Alameh7Drew Weissman8Gary H. Cohen9Harvey M. Friedman10Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAAcuitas Therapeutics Inc., Vancouver, BC V6T 1Z3, CanadaInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAInfectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAHSV-1 disease is a significant public health burden causing orofacial, genital, cornea, and brain infection. We previously reported that a trivalent HSV-2 gC2, gD2, gE2 nucleoside-modified mRNA-lipid nanoparticle (LNP) vaccine provides excellent protection against vaginal HSV-1 infection in mice. Here, we evaluated whether this HSV-2 gC2, gD2, gE2 vaccine is as effective as a similar HSV-1 mRNA LNP vaccine containing gC1, gD1, and gE1 in the murine lip and genital infection models. Mice were immunized twice with a total mRNA dose of 1 or 10 µg. The two vaccines produced comparable HSV-1 neutralizing antibody titers, and surprisingly, the HSV-2 vaccine stimulated more potent CD8<sup>+</sup> T-cell responses to gE1 peptides than the HSV-1 vaccine. Both vaccines provided complete protection from clinical disease in the lip model, while in the genital model, both vaccines prevented death and genital disease, but the HSV-1 vaccine reduced day two vaginal titers slightly better at the 1 µg dose. Both vaccines prevented HSV-1 DNA from reaching the trigeminal or dorsal root ganglia to a similar extent. We conclude that the trivalent HSV-2 mRNA vaccine provides outstanding protection against HSV-1 challenge at two sites and may serve as a universal prophylactic vaccine for HSV-1 and HSV-2.https://www.mdpi.com/1999-4915/15/7/1483HSV-1HSV-2HSV vaccinenucleoside-modified mRNAoral herpesgenital herpes |
| spellingShingle | Kevin P. Egan Sita Awasthi Giulia Tebaldi Lauren M. Hook Alexis M. Naughton Bernard T. Fowler Mitchell Beattie Mohamad-Gabriel Alameh Drew Weissman Gary H. Cohen Harvey M. Friedman A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1 Viruses HSV-1 HSV-2 HSV vaccine nucleoside-modified mRNA oral herpes genital herpes |
| title | A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1 |
| title_full | A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1 |
| title_fullStr | A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1 |
| title_full_unstemmed | A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1 |
| title_short | A Trivalent HSV-2 gC2, gD2, gE2 Nucleoside-Modified mRNA-LNP Vaccine Provides Outstanding Protection in Mice against Genital and Non-Genital HSV-1 Infection, Comparable to the Same Antigens Derived from HSV-1 |
| title_sort | trivalent hsv 2 gc2 gd2 ge2 nucleoside modified mrna lnp vaccine provides outstanding protection in mice against genital and non genital hsv 1 infection comparable to the same antigens derived from hsv 1 |
| topic | HSV-1 HSV-2 HSV vaccine nucleoside-modified mRNA oral herpes genital herpes |
| url | https://www.mdpi.com/1999-4915/15/7/1483 |
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