Herpes simplex virus type-2 (HSV-2) is a common pathogen with a seroprevalence rate that has been increasing in the US over the last several years. There is no vaccine or effective microbicide available against the virus. Apart from the discomfort associated with the symptomatic disease which results in genital ulcers, asymptomatic shedding greatly enhances person-to-person virus transmission. HSV-2 also enhances susceptibility to human immunodeficiency virus (HIV) by 2-3 folds. Therefore, there is an urgent need for a strong microbicide and an effective vaccine. In this proposal we plan to explore the idea of developing a unique non-invasive mucosal microbicide/vaccine combo which initially functions as a microbicide by effectively trapping HSV-2 virions and rendering them non-infective and then provides a unique viral antigen displaying platform for the mucosal antigen presenting cells for processing, presentation, and induction of immunity. This novel platform is based on our uniquely designed zinc oxide micro-nano spike particles (ZnO-MNPs), which trap HSV virions with very high efficacy. The trapping, which concentrates the virions at one place, renders them unable to enter cells. We propose that high concentrations of trapped virions on ZnO-MNPs will elicit a very strong immune response without the need of any additional adjuvant, since ZnO is already shown to have good adjuvant properties. Another added advantage of our microbicide/vaccine combo is that Zinc oxide is already used in common cosmetic products. Two exploratory Aims are proposed.
Aim 1 will test the hypothesis that ZnO-MNPs can act as an effective microbicide by preventing virus attachment to host cells in vivo.
Aim 2 will test the hypothesis that HSV-2 virions trapped by ZnO-MNPs can be recognized by mucosal antigen presenting cells and processed for immunity development. Overall, we expect to prove the vaccine efficacy of a new virostatic platform, which will have path defining implications for protection against HSV-2 and many additional viral diseases.
Herpes simplex virus type-2 (HSV-2) causes genital infection and it is a co-factor in the acquisition of human immunodeficiency virus (HIV). Currently there is no vaccine available to control human-to-human transmission of this virus, which can happen without any initial symptoms. We propose to test a novel virus- trapping microbicide using specially synthesized zinc oxide micro-nano particles, which we expect will prevent infection and at the same time, also act as a vaccine by displaying the trapped virus particles for mucosal immunity development. This non-invasive, topical microbicide/vaccine combo, if proven effective, will pave the way for similar prophylactic strategies against multiple microbial disease including sexually transmitted viral infections.
| Yadavalli, Tejabhiram; Shukla, Deepak (2017) Role of metal and metal oxide nanoparticles as diagnostic and therapeutic tools for highly prevalent viral infections. Nanomedicine 13:219-230 |
| Antoine, Thessicar E; Hadigal, Satvik R; Yakoub, Abraam M et al. (2016) Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes. J Immunol 196:4566-75 |
| Hadigal, Satvik R; Agelidis, Alex M; Karasneh, Ghadah A et al. (2015) Heparanase is a host enzyme required for herpes simplex virus-1 release from cells. Nat Commun 6:6985 |
| Coleman, Jeffrey L; Shukla, Deepak (2013) Recent advances in vaccine development for herpes simplex virus types I and II. Hum Vaccin Immunother 9:729-35 |
| Hadigal, Satvik; Shukla, Deepak (2013) Exploiting herpes simplex virus entry for novel therapeutics. Viruses 5:1447-65 |
