Pathogens often rely on contact between host organisms for transmission. Many pathogens have adapted their transmission mechanisms to take advantage of behaviours that are essential for the survival of the host species, such as eating (oral), breathing (respiratory) and procreating (genital), whereas others use insect vectors to inoculate themselves into their mammalian hosts. Some pathogens have evolved to exploit sexual contact of the host organism for their transmission. Transmission of this class of pathogen that causes sexually transmitted infections (STIs) depends on the sexual maturity and promiscuity of humans. The World Health Organization (WHO) estimates that one million new cases of STIs occur every day. Yet, for the most part, vaccines that prevent STIs are not available.
Compared to the intestinal mucosa, the female and male genital tracts are covered by distinct epithelial cell layers and mucus types, are inhabited by a unique set of microbial flora, and use distinct innate and adaptive effector mechanisms. Unlike STIs caused by bacterial pathogens, which are treatable by antibiotics, there are no cures for viral STIs. Currently available antiviral agents are unable to eliminate the latent pool of viruses such as HIV-1 or HSV. This review is not intended to be a comprehensive overview of vaccines against STIs. Instead, in this review I use examples of three major human sexually transmitted viral pathogens – HIV-1, human papillomavirus (HPV) and herpes simplex virus type 2 (HSV-2) – to describe our current understanding of modes of viral entry, innate detection, initiation of adaptive immune responses and virus clearance. Further, I discuss how understanding the innate and adaptive immune mechanisms of protection in the genital mucosa could be applied for rational design of vaccines against STIs.