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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. A vaccine strategy that protects against genital herpes by establishing local memory T cells appears in Nature.

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.

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