Herpes Simplex Type 2 Virus Deleted in Glycoprotein D Protects Against Vaginal, Skin and Neural Disease

Overview

Journal Elife

Specialty Biology

Date 2015 Mar 11

PMID 25756612

Citations 75

Authors

Christopher Petro

Pablo A Gonzalez

Natalia Cheshenko

Thomas Jandl

Nazanin Khajoueinejad

Angele Benard

Mayami Sengupta

Betsy C Herold

William R Jacobs

Affiliations

Soon will be listed here.

Abstract

Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (ΔgD(-/+gD-1)). Subcutaneous immunization of C57BL/6 or BALB/c mice with ΔgD(-/+gD1) provided 100% protection against lethal intravaginal or skin challenges and prevented latency. ΔgD(-/+gD1) elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fcγ-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.

Citing Articles

A nonhuman primate model for genital herpes simplex virus 2 infection that results in vaginal vesicular lesions, virus shedding, and seroconversion.

Wang K, Jordan T, Dowdell K, Herbert R, Moore I, Koelle D PLoS Pathog. 2024; 20(9):e1012477.

PMID: 39226323 PMC: 11371218. DOI: 10.1371/journal.ppat.1012477.

Summary of the Centers for Disease Control and Prevention/National Institute of Allergy and Infectious Diseases Joint Workshop on Genital Herpes: 3-4 November 2022.

Connolly K, Bachmann L, Hiltke T, Kersh E, Newman L, Wilson L Open Forum Infect Dis. 2024; 11(5):ofae230.

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The Interplay of Genital Herpes with Cellular Processes: A Pathogenesis and Therapeutic Perspective.

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Greater Durability and Protection against Herpes Simplex Viral Disease following Immunization of Mice with Single-Cycle ΔgD-2 Compared to an Adjuvanted Glycoprotein D Protein Vaccine.

Mahant A, Gromisch M, Kravets L, Aschner C, Herold B Vaccines (Basel). 2023; 11(8).

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