Estradiol and MDMA affect the susceptibility and immune response to genital herpes and genital herpes immunization
Jeffry Warren Pennock
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Herpes simplex virus type 2 (HSV-2), the most frequent cause of ulcerative genital herpes disease, has infected nearly one-in-five Americans and is even more prevalent in the developing world. The virus is also known to be a synergistic copathogen to HIV and may even facilitate its infection. Nonetheless, the vast majority of HSV-2-infected patients are unaware of their infection and are capable of asymptomatically transmitting the virus during sexual contact, thus a prophylactic vaccine is needed. Therefore, the research presented here examines a factor that could be important in enhancing susceptibility to genital herpes disease as well as one that could be important in enhancing vaccine-afforded protection against it. There is no HSV-2 prophylactic vaccine currently available but there is a subunit vaccine candidate in clinical trials which has shown efficacy in preventing disease in women. Using this vaccine candidate, we were able to demonstrate infection prophylaxis, improved disease prevention and modulated antibody production by complimenting vaccination with estradiol in a murine model. We also showed the effects of estradiol on vaccine efficacy in a guinea pig model. Findings of estradiol-enhanced vaccine efficacy are the first of their kind using a vaccine of this type and have potential clinical relevance to the development of other vaccines, as well as our understanding of gender differences in vaccine efficacy. Meanwhile, 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”) was abused by over 1.2 million Americans in 2007 and is popular in the dance club, rave and circuit party scenes. MDMA and other similar drugs are reportedly associated with increased incidence of sexually transmitted infections, like HIV or genital herpes, and may have immunological effects. We were able to demonstrate that MDMA causes increased susceptibility to HSV-2 infection in mice and earlier onset of genital herpes disease. We also demonstrated an MDMA-effect on the cytokines of the innate immune system, both systemically and, for the first time, in the genital tract. These data suggest MDMA may have an important biological role in infection and that estradiol may have an important role in vaccine-elicited protection against it.