Radical Vaccine Design Effective Against Herpes Viruses

Radical Vaccine Design Effective Against Herpes Viruses
Micrograph showing the viral cytopathic effect of HSV (multi-
nucleation, ground glass chromatin). (Credit: Wikipedia)
Herpes simplex virus infections are an enormous global health problem and there is currently no viable vaccine. For nearly three decades, immunologists' efforts to develop a herpes vaccine have centered on exploiting a single protein found on the virus's outer surface that is known to elicit robust production of antibodies. Breaking from this approach, researchers have created a genetic mutant lacking that protein. The result is a powerfully effective vaccine against herpes viruses.
 
The new vaccine was found to be effective against the two most common forms of herpes that cause cold sores (HSV-1) and genital ulcers (HSV-2). Both are known to infect the body's nerve cells, where the virus can lay dormant for years before symptoms reappear. The new vaccine is the first to prevent this type of latent infection. The findings are published in the journal eLife.
 
HSV-2 is a lifelong, incurable infection that causes recurrent and painful genital sores and increases susceptibility to HIV. Also, babies born to mothers with active genital herpes have a more than 80 percent mortality rate. Current estimates suggest that 500 million people worldwide are infected with HSV-2, with approximately 20 million new cases occurring annually. While infection rates in the U.S. hover around 15 to 20 percent, HSV-2 is highly prevalent in sub-Saharan Africa, where nearly three in four women have contracted the virus, contributing significantly to the region's HIV epidemic. The related virus, HSV-1 is primarily associated with oral lesions, but is a major cause of corneal blindness and infects around 60 percent of the world's population. Notably, HSV-1 has been increasingly recognized as a cause of genital herpes in the United States and other developed countries.
 
The vaccine completely immunized two common strains of lab mice against HSV-2 when challenged with virus intravaginally or on the skin. In fact, no virus could be detected in vaginal washes four days post-challenge and even more importantly, no virus could be found in the nerve tissue, the site where HSV often hides in a latent form only to emerge later to cause disease. Protection against HSV-1, which shares considerable homology with HSV-2, was also demonstrated in both models. The vaccine produced no adverse health effects in a strain of mice with severely compromised immune systems, reflecting the vaccine's overall safety.
 
Blood serum passively transferred from immunized mice was found to protect wild-type mice, providing a powerful demonstration of the vaccine's efficacy.
 
Another of the vaccine's surprises is how it works. Many vaccines provoke the production of so-called neutralizing antibodies that directly bind and inactivate virus particles. The new vaccine, however, induces antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibodies attach to a virus and flag it for destruction by immune system sentinels such as white blood cells.
 
The robust response generated by the vaccine, as well as its novel mechanism, has the researchers undertaking additional experiments in mice to determine whether it can be used to treat individuals already infected by HSV-1 and HSV-2.
 
The next step for the researchers in producing a herpes vaccine for use in humans is demonstrating its efficacy and safety in an FDA-approved cell line.
 
Based on material originally posted by Howard Hughes Medical Institute.
 
The paper is titled "Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease." The other contributors are: Christopher Petro, Ph.D., Pablo A. González, Ph.D., Natalia Cheshenko, Ph.D., Thomas Jandl, Ph.D., Nazanin Khajoueinejad, Angèle Bénard, Ph.D., and Mayami Sengupta, Ph.D., all at Einstein.