Herpes simplex virus-2, which causes serious eye infections in newborns and immunocompromised patients as well as genital herpes, is one of the most common human viruses. According to the Centers for Disease Control and Prevention, about 15% of people from ages 14-49 carry HSV-2, which can hide out for long periods of time in the nervous system. It is known that the genital lesions caused by the virus also increase the risk for acquiring human immunodeficiency virus, or HIV. The chances of getting HIV are three to four times higher if a person already has genital herpes, which is a very strong motivation for developing new ways of preventing herpes infection.
However, an effective vaccine against the virus that causes genital herpes has evaded researchers for decades. Now, a study from researchers at the University of Illinois and Kiel University shows that zinc-oxide nanoparticles shaped like jacks can prevent the virus from entering cells, and help a natural immunity to develop. The team state that the particles could serve as a powerful active ingredient in a topically-applied vaginal cream that provides immediate protection against herpes virus infection while simultaneously helping stimulate immunity to the virus for long-term protection. The study is published in The Journal of Immunology.
Previous studies show that 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. The current study describes a tetrapod-shaped zinc-oxide nanoparticle, called ZOTEN, with negatively charged surfaces that attract the HSV-2 virus, which has positively charged proteins on its outer envelope.
The current study developed ZOTEN nanoparticles, virus-trapping nanoparticles named microbivacs by the lab, as they possess both microbicidal and vaccine-like properties. Results show that when bound to the nanoparticles, HSV-2 cannot infect cells with the bound virus remaining susceptible to processing by immune cells called dendritic cells that patrol the vaginal lining. Data findings show that the dendritic cells ‘present’ the virus to other immune cells that produce antibodies, the antibodies then cripple the virus and trigger the production of customized killer cells that identify infected cells and destroy them before the virus can take over and spread.
Results show that female mice swabbed with HSV-2 and an ointment containing ZOTEN had significantly fewer genital lesions than mice treated with a cream lacking ZOTEN. Data findings show that mice treated with ZOTEN also had less inflammation in the central nervous system, where the virus can hide out.
The group then pried immune cells and the attached virus off the nanoparticles for immune processing, using high-resolution fluorescence microscopy. They observed that ZOTEN facilitates the development of immunity by holding the virus and allowing dendritic cells to access it. They researchers state that ZOTEN particles are uniform in size and shape, making them attractive for use in other biomedical applications. They go on to add that the novel flame transport synthesis technology used to make them allows large-scale production and, because no chemicals are used, the production process is green.
The team surmise that their findings provide the very first evidence for the protective efficacy of an intravaginal microbicide/vaccine or microbivac platform against primary and secondary female genital herpes infections. For the future, the researchers state that if found safe and effective in humans, a ZOTEN-containing cream ideally would be applied vaginally just prior to intercourse. They go on to add that if a woman who had been using it regularly missed an application, she may have already developed some immunity and still have some protection.