A “Prime” New Strategy for Herpes Vaccination

Genital herpes currently affects up to one in six Americans between the ages of 14 and 49, yet no vaccine or cure for this, common sexually transmitted infection (STI) exists. However, a recent paper by Yale professor Akiko Iwasaki and postdoctoral fellow Haina Shin published in Nature reports a promising new vaccine strategy termed “prime and pull” that could easily and effectively protect against the main cause of genital herpes, herpes simplex virus 2 (HSV-2).

Normally, vaccines provide protection by introducing a weakened version of a pathogen. The body’s B cells, a type of white blood cell, then produce antibodies targeting the invader, which prepares the immune system to respond quickly to future infection. However, Iwasaki learned “from many years of people trying to vaccinate against HSV that an antibody-based vaccine alone is not effective.”

The herpes virus first infects epithelial cells before invading the neurons, where it remains latent until later reactivated by hormones or stress. Courtesy of the Davidson College Biology Department.

To get around this issue, the researchers designed a method that would allow another type of white blood cell, the T cell, to get to the site of infection and provide protection. T cells have already been shown to play a role in controlling HSV-2 but have limited access to the genital tract, which prevents their entry in the absence of inflammation or infection. Therefore, it seemed likely that T cells would be even more effective when immediately moved to the infected tissue.

The first step of this process, or the “prime,” involves a conventional vaccination with weakened HSV-2, which activates HSV-2-specific T cells throughout the body. Then, in the second step, the activated T cells are “pulled” to the genital tract by topical application of chemokines, substances that attract immune cells.

This prime and pull strategy has proved very effective against HSV-2. Mice treated with the method had increased survival rates, as compared to mice given the immunization (prime) without the chemokine pull, and did not develop clinical herpes when infected with the virus.

In addition to effective protection, the prime and pull immunization also causes little to no inflammation in the genital tract, a problem which had plagued previous vaccine models that fought herpes. “In terms of safety, [prime and pull] is a much better approach,” says Iwasaki.

While the immunization is surprisingly effective, researchers are still working to understand exactly how it works. At first, the T cells were expected to attack infected cells in the vaginal lining, but as Iwasaki explains, “our data showed that the protection is really at the level of the neuron.” Specifically, the T cells are hypothesized to prevent virus entry into neurons, where HSV-2 would otherwise remain dormant and cause recurring outbreaks. If T cells can indeed prevent the virus from getting into the nervous system, Iwasaki adds, the vaccination “can hopefully provide protection for life.”.

In addition to a vaccine against genital herpes, the prime and pull method has many other promising applications. It could be useful in any situation in which T cells are required locally, such as in preventing HIV and other STIs, or even in treatment of solid tumors. In the future, Iwasaki would like to see other researchers use the method both for their own applications and for making the new herpes vaccine clinically available.

The researchers’ “prime and pull” immunization brings T cells, pictured here in a scanning electron micrograph, to the site of infection, allowing for effective vaccination. Courtesy of the MIT Technology Review.