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

Fingerprint

Immunization
Human Herpesvirus 2
Viruses
Skin Diseases
Glycoproteins
Skin
Attenuated Vaccines
Subunit Vaccines
SCID Mice
Fc Receptors
Antibodies
Human Herpesvirus 1
Cytotoxicity
Knockout Mice
Immune Sera
Cells
Safety
Antigens
Serum
neonatal Fc receptors

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease. / Petro, Christopher; González, Pablo A.; Cheshenko, Natalia; Jandl, Thomas; Khajoueinejad, Nazanin; Bénard, Angèle; Sengupta, Mayami; Herold, Betsy C.; Jacobs, William R.

In: eLife, Vol. 4, 2015.

Research output: Contribution to journalArticle

Petro, Christopher ; González, Pablo A. ; Cheshenko, Natalia ; Jandl, Thomas ; Khajoueinejad, Nazanin ; Bénard, Angèle ; Sengupta, Mayami ; Herold, Betsy C. ; Jacobs, William R. / Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease. In: eLife. 2015 ; Vol. 4.
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