New Approach to Vaccinating Against Genital Herpes Holds Promise

A recent study in mice has shown that specially-designed zinc oxide tetrapod nanoparticles (ZOTEN) could hold promise as a novel method of vaccinating against herpes simplex-2 virus (HSV-2).

Thessicar E. Antoine, PhD, from the University of Illinois, Chicago, and colleagues published the results of their study in The Journal of Immunology.

“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 authors write. “The strong HSV-2 trapping ability of ZOTEN significantly reduced the clinical signs of vaginal infection and effectively decreased animal mortality.”

HSV-2 infection is typically sexually transmitted and causes genital herpes, which is characterized by intermittent viral shedding and periodic appearance of painful genital ulcers which also increase the person’s risk of acquiring human immunodeficiency virus (HIV) infection. Affected individuals also frequently experience significant psychological and emotional effects as a result of the disease. Infection with HSV-2 is also lifelong and contributes to a substantial disease burden worldwide. Indeed, a recent report estimated that more than 400 million people globally had HSV-2 infection.

Although this highlights the critical need for development of strategies to prevent HSV-2 infection, an effective vaccine against HSV-2 has been hard to find. According to the authors, this is because HSV-2 does not remain in the bloodstream where vaccines are most effective. As a consequence, treatment of people with genital herpes is currently limited to the use of topical medications that suppress the virus and shorten the duration of flare-ups. However, resistance to these drugs is common.

With this in mind, Dr. Antoine and colleagues conducted a study to investigate the use of ZOTEN as a strategy to protect against genital herpes in female mice with HSV-2 infection.

First, they swabbed the mice with HSV-2. Next, they treated some with ZOTEN ointment, and the remainder with placebo ointment. The ZOTEN-treated mice developed significantly fewer genital lesions than the placebo-treated mice did, and also had less inflammation in the central nervous system, where the virus can hide.

In an interview podcast, the study’s corresponding author, Deepak Shukla, PhD, also from the University of Illinois, Chicago, explained how the zinc oxide nanoparticles work in the body. He noted that the nanoparticles—which are shaped like jacks—work through attraction of electrical charges. “The ZOTEN have negatively charged surfaces that attract the HSV-2 virus, which has positively charged proteins on its outer envelope.”

As a result of this attraction, when HSV-2 becomes bound to the nanoparticles, it cannot infect cells because the nanoparticle-virus complex is too large to pass through the cell membrane into the cell. However, the bound virus does remain susceptible to attack by dendritic cells of the immune system, thereby stimulating a specific antibody response against HSV-2, as well as production of immune cells that destroy HSV-2-infected cells to prevent further viral spread. “We call this virus-trapping nanoparticle a microbivac, because it possesses both microbicidal and vaccine-like properties,” said Dr Shukla. “If ZOTEN is proven to be safe and effective in humans, a ZOTEN-containing cream would ideally be applied vaginally just prior to intercourse.”

Overall, the authors conclude that this 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.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.