EXECUTIVE SUMMARY
Researchers from the University of Illinois at Chicago, working with scientists from Germany, have shown that zinc oxide nanoparticles can prevent the herpes simplex virus from entering cells.
- Based on their recent findings, the scientists believe the particles could serve as a powerful active ingredient in a topically applied vaginal cream that would provide immediate protection against herpes virus infection while simultaneously helping stimulate immunity to the virus for long-term protection.
- Research also is moving ahead on treatment of genital herpes. Recently released results of a Phase II clinical trial indicate that a new type of treatment for genital herpes, an immunotherapy called GEN-003, may reduce the activity of the virus and the number of days with recurrent herpes.
Researchers from the University of Illinois at Chicago, working with scientists from Germany, have shown that zinc oxide nanoparticles can prevent the herpes simplex virus from entering cells.
Based on their recent findings, the scientists believe that the particles could serve as a powerful active ingredient in a vaginal cream, which would be applied topically, that would provide immediate protection against herpes virus infection while simultaneously helping stimulate immunity to the virus for long-term protection.1
Virtually all efforts to generate an effective protection against the lifelong, recurrent genital infections caused by HSV-2 have failed. Apart from sexual transmission, the virus also can be transmitted from mothers to neonates, and it is a key facilitator of HIV coacquisition.1
“We call the virus-trapping nanoparticle a microbivac, because it possesses both microbicidal and vaccine-like properties,” says Deepak Shukla, PhD, professor of ophthalmology and microbiology & immunology in the University of Chicago College of Medicine and lead author of the current paper. “It is a totally novel approach to developing a vaccine against herpes, and it could potentially also work for HIV and other viruses.”
How it works
The tetrapod-shaped zinc-oxide nanoparticles, which are called ZOTEN by University of Chicago researchers, work through basic electrical charges.
The ZOTEN have negatively charged surfaces that attract the HSV-2 virus, which has positively charged proteins on its outer envelope, explains Shukla. When the herpes virus is bound to the nanoparticles, it cannot infect cells, because the nanoparticle/virus complex is too large to pass through the cell membrane.
The bound virus also is exposed to processing by immune cells, known as dendritic cells, that patrol the vaginal lining. The dendritic cells overtake and process the virus, presenting pieces of it to the immune cells that produce antibodies specific to the herpes virus. The antibodies then deactivate the virus and trigger the production of customized killer cells that identify infected cells and destroy them before those cells are able to spread.1
The particles potentially could serve as a powerful active ingredient in a topically applied vaginal cream that would provide immediate protection against herpes virus infection while simultaneously helping stimulate immunity to the virus for long-term protection, explains Shukla.
Anita Nelson, MD, professor emeritus in the Obstetrics and Gynecology Department at the David Geffen School of Medicine at the University of California in Los Angeles, says, “Beyond the science of whether zinc oxide works or not, I think that any research in this area may have profound implications for the work on HIV prevention strategies using PrEP/PEP [pre-exposure prophylaxis/post-exposure prophylaxis]. Will at-risk women really consistently use something to prevent HSV infection? Will they be motivated to protect themselves from HSV better than they use contraception or PrEP/PEP?”
Vaccine in the pipeline
Research also is moving ahead on treatment of genital herpes. Recently released results of a Phase II clinical trial indicate that a new type of treatment for genital herpes, an immunotherapy called GEN-003, may reduce the activity of the virus and the number of days with recurrent herpes.2 This novel treatment, given by three injections, appears to last for up to at least one year, according to research presented at the 2016 microbe research meeting of the American Society for Microbiology.2
Kenneth Fife, MD, PhD, an investigator and professor of medicine at Indiana University in Indianapolis, said, “GEN-003 is believed to work through a different pathway from most vaccines by recruiting T cells, which are critical to controlling chronic infections such as herpes. In addition, GEN-003 is also designed to stimulate antibodies to help neutralize the virus.”
To conduct the current study, 310 participants with a history of chronic, recurrent genital herpes received three shots of one of six vaccine doses, 21 days apart. Over one year, participants were tested for stimulation of the immune system against the herpes virus, the frequency that the herpes virus was detectable on the skin around the genital area (“viral shedding”), and the number of days that herpes outbreaks (“lesions”) were visible.
Data indicate the GEN-003 treatment resulted in reductions in the rate of viral shedding and lesion frequency compared to rates before treatment. Immune response data are being analyzed and will be the topic of a future presentation.2
The GEN-003 vaccine is a first-in-class immunotherapy composed of two immunogenic antigens and a matrix adjuvant, designed to induce T-cell and B-cell immune responses. The vaccine is under development by Genocea Biosciences of Cambridge, MA.
Treatments for HSV-2 include daily topical medications to suppress the virus and shorten the duration of outbreaks, when the virus is active and genital lesions are present. However, drug resistance is common, and little protection is provided against further infections. Efforts to develop a vaccine have been unsuccessful because the virus does not spend much time in the bloodstream, where most traditional vaccines do their work.
REFERENCES
- Antoine TE, Hadigal SR, Yakoub AM, et al. Intravaginal zinc oxide tetrapod nanoparticles as novel immunoprotective agents against genital herpes. J Immunol 2016; 196(11):4566-4575.
- American Society for Microbiology. A novel therapy for genital herpes engages immune cells to provide significant patient benefits for at least a year. Press release. Accessed at http://bit.ly/29PPNkF.
