"Cross protective efficacy of the Non-Neurotropic live attenuated herpe" by Brent A. Stanfield, Fernando J. Bravo et al.

Faculty Publications

Title

Cross protective efficacy of the Non-Neurotropic live attenuated herpes simplex virus type 1 vaccine VC-2 is enhanced by intradermal vaccination and deletion of glycoprotein G

Authors

Brent A. Stanfield, Division of Biotechnology and Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Fernando J. Bravo, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
David A. Dixon, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
Vladimir N. Chouljenko, Division of Biotechnology and Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
Konstantin G. Kousoulas, Division of Biotechnology and Molecular Medicine and Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
David I. Bernstein, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA. Electronic address: david.bernstein@cchmc.org.

Document Type

Article

Publication Date

10-6-2022

Abstract

Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2 respectively) cause life-long latent infections resulting in recurrent orofacial and genital blisters or sores. Ensued disease can be painful and may lead to significant mental anguish of infected individuals. Currently, there are no FDA-approved vaccines for either prophylactic or therapeutic use, and recent clinical trials of subunit vaccines failed to achieve endpoints goals. Development of a safe live-attenuated herpes simplex vaccine may provide the antigenic breadth to ultimately protect individuals from acquiring HSV disease. We have previously shown that prophylactic use of the non-neurotropic live attenuated HSV-1 vaccine, VC-2, provides potent and durable protection from genital HSV-2 disease in the guinea pig model. Here, we investigated the effects of intradermal administration as well as the deletion of the viral glycoprotein G (gG) on the efficacy of prophylactic vaccination. Vaccination with either VC-2, VC-2 gG null, or gD2 MPL/Alum offered robust protection from acute disease regardless of route of vaccination. However, both the VC-2 gG-null and the ID vaccination route were more effective compared to the parent VC2 administered by the IM route. Specifically, the VC-2 gG-null administered ID, reduced HSV-2 vaginal replication on day 2 and day 4 as well as mean recurrent lesion scores more effectively than VC2 administered IM. Most importantly, only VC-2 gG null IM and VC-2 ID significantly reduced the frequency of recurrent shedding, the most likely source for virus transmission. Similarly, while all vaccinated groups demonstrated a significant reduction in the number of animals testing PCR-positive for HSV-2 in their dorsal root ganglia following challenge only VC2 ID vaccinated animals demonstrated a significant reduction in DRG viral load. All vaccinations induced neutralizing antibodies to HSV-2 MS when compared to unvaccinated guinea pigs. Therefore, further investigation of VC-2 gG null delivered ID is warranted.

Publication Source (Journal or Book title)

Vaccine

First Page

6093

Last Page

6099

Recommended Citation

Stanfield, B. A., Bravo, F. J., Dixon, D. A., Chouljenko, V. N., Kousoulas, K. G., & Bernstein, D. I. (2022). Cross protective efficacy of the Non-Neurotropic live attenuated herpes simplex virus type 1 vaccine VC-2 is enhanced by intradermal vaccination and deletion of glycoprotein G. Vaccine, 40 (42), 6093-6099. https://doi.org/10.1016/j.vaccine.2022.09.015

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