Genital herpes: Yale researchers develop vaccine strategy

Yale researchers have developed a new model for vaccination against genital herpes, a disease for which there has been no cure and no effective immunization. Their study appears in the Advance Online Publication of Nature.

Genital herpes, known formally as herpes simplex virus (HSV), is a mostly sexually transmitted infection (STI) that accounts for significant disease and morbidity.

Until now, most efforts to develop a vaccine have focused on the immune system’s antibodies, or T cells, circulating through the body. When T cells encounter foreign invaders such as bacteria or viruses, they learn to recognize them and mount ever-stronger immune responses to fight them. But efforts to harness these circulating T cells have not been effective in organs such as the vagina, intestines, lung airways, and central nervous system, which restrict the entry of these “memory” T cells.

To investigate an alternative approach, the Yale team focused instead on peripheral tissue in the female genital tract, where viral exposure occurs. The challenge was to recruit virus-specific T cells into the vaginal mucosa without triggering a potentially harmful inflammatory response of the immune system.

Working with mice, they explored a two-part vaccine strategy they call “prime and pull.” The “priming” involved conventional vaccination to elicit a system-wide T cell response. The “pulling” involved recruitment of activated T cells directly into the vaginal tissue, via topical application, of chemokines — substances that help mobilize the immune cells.

They found that the recruited T cells were able to establish a long-term niche and offer protective immunity against genital herpes by reducing the spread of HSV into the sensory neurons.

The Yale team’s new vaccination model may offer a promising vaccination strategy against not just HSV, but potentially other STIs such as HIV-1. “This new vaccine approach can work with any vaccines that elicit strong T cell immunity, and will set the stage for protection against infectious diseases by setting up memory T-cells at the site of exposure,” said lead author Akiko Iwasaki, professor of immunobiology at Yale School of Medicine and a member of Yale Cancer Center’s molecular virology program.

“This technology can be potentially applied to other infectious agents that enter through a given portal, such as the genital tract, respiratory tract, the skin, or gut,” she added.

Co-author is Haina Shin of Yale School of Medicine. The study was supported by grants from the National Institutes of Health.