Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes

J Immunol. 2016 Jun 1;196(11):4566-75. doi: 10.4049/jimmunol.1502373. Epub 2016 Apr 27.

Abstract

Virtually all efforts to generate an effective protection against the life-long, recurrent genital infections caused by HSV-2 have failed. Apart from sexual transmission, the virus can also be transmitted from mothers to neonates, and it is a key facilitator of HIV coacquisition. In this article, we uncover a nanoimmunotherapy using specially designed zinc oxide tetrapod nanoparticles (ZOTEN) with engineered oxygen vacancies. We demonstrate that ZOTEN, when used intravaginally as a microbicide, is an effective suppressor of HSV-2 genital infection in female BALB/c mice. The strong HSV-2 trapping ability of ZOTEN significantly reduced the clinical signs of vaginal infection and effectively decreased animal mortality. In parallel, ZOTEN promoted the presentation of bound HSV-2 virions to mucosal APCs, enhancing T cell-mediated and Ab-mediated responses to the infection, and thereby suppressing a reinfection. We also found that ZOTEN exhibits strong adjuvant-like properties, which is highly comparable with alum, a commonly used adjuvant. Overall, to our knowledge, our study provides the very first evidence for the protective efficacy of an intravaginal microbicide/vaccine or microbivac platform against primary and secondary female genital herpes infections.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chlorocebus aethiops
  • Female
  • HeLa Cells
  • Herpes Genitalis / drug therapy*
  • Herpes Genitalis / immunology*
  • Herpes Genitalis / pathology
  • Herpesvirus 2, Human / drug effects*
  • Herpesvirus 2, Human / immunology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use*
  • Particle Size
  • Structure-Activity Relationship
  • Vero Cells
  • Zinc Oxide / administration & dosage*
  • Zinc Oxide / pharmacology
  • Zinc Oxide / therapeutic use*

Substances

  • Zinc Oxide