Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease

Christopher Petro, Pablo A. González, Natalia Cheshenko, Thomas Jandl, Nazanin Khajoueinejad, Angèle Bénard, Mayami Sengupta, Betsy C. Herold, William R. Jacobs

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournaleLife
Volume4
DOIs
StatePublished - 2015

Keywords

  • antibody
  • HSV-2
  • immunity
  • infectious disease
  • microbiology
  • mouse
  • vaccine
  • virology

ASJC Scopus subject areas

  • Medicine(all)

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