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, Howard Hughes Medical Institute (HHMI) scientists at Albert Einstein College of Medicine have created a genetic mutant lacking that protein. The result is a powerfully effective vaccine against herpes viruses.
“We have a very promising new candidate for herpes,” says William Jacobs, an HHMI investigator at the Albert Einstein College of Medicine, “but this might also be a good candidate as a vaccine vector for other mucosal diseases, particularly HIV and tuberculosis.”
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. “With herpes sores you continually get them,” Jacobs says. “If our vaccine works in humans as it does in mice, administering it early in life could completely eliminate herpes latency.” Jacobs and his colleagues reported their findings 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.
Most prior attempts to construct a herpes vaccine have focused on a glycoprotein called gD that is embedded in the virus’s outer envelope. This protein is required for the microbe to enter into and out of cells and to spread from cell-to-cell gD also elicits a vigorous antibody response that many in the field believe is necessary to produce immunity. However, no gD-based vaccine has proven effective.