title: Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes.
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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612; Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;
authors.forename: Thessicar E
authors.identifier: 0000-0002-9049-4301
authors.initials: TE
authors.lastname: Antoine
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612;
authors.forename: Satvik R
authors.initials: SR
authors.lastname: Hadigal
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612; Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;
authors.forename: Abraam M
authors.initials: AM
authors.lastname: Yakoub
authors.affiliation: Institute for Materials Science, Kiel University, Kiel 24143, Germany; and.
authors.forename: Yogendra Kumar
authors.identifier: 0000-0002-8786-9379
authors.initials: YK
authors.lastname: Mishra
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;
authors.forename: Palash
authors.initials: P
authors.lastname: Bhattacharya
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;
authors.forename: Christine
authors.initials: C
authors.lastname: Haddad
authors.affiliation: Department of Pathology, University of Illinois, Chicago, IL 60612.
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.affiliation: Institute for Materials Science, Kiel University, Kiel 24143, Germany; and.
authors.forename: Rainer
authors.initials: R
authors.lastname: Adelung
authors.affiliation: Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612;
authors.forename: Bellur S
authors.identifier: 0000-0001-9815-9850
authors.initials: BS
authors.lastname: Prabhakar
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, IL 60612; Department of Microbiology and Immunology, University of Illinois, Chicago, IL 60612; dshukla@uic.edu.
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D005260:Female; D006367:HeLa Cells; D006558:Herpes Genitalis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D010316:Particle Size; D013329:Structure-Activity Relationship; D014709:Vero Cells; D015034:Zinc Oxide / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015034:Zinc Oxide