Vaccines against genital herpes: progress and limitations

Herpes simplex viruses (HSV) cause lifelong persistent infections with numerous disease manifestations. Genital herpes infections are widespread in populations throughout the world and a vaccine to protect against or subdue established genital herpes infections has been under development for decades. Vaccine-mediated protection against persistent viral infections can be extremely difficult to achieve. The more rapidly a virus reaches its target tissue for persistence, the more vigorously a vaccine-induced immune response must defend the vaccinated individual. After exposure to HSV through sexual contact, only a few days are required for the virus to establish latent infection of its host. Despite numerous improvements, traditional vaccine approaches of whole virus or protein subunits have met with only marginal success. The many disappointments have heightened interest in determining correlates of immune protection, studies pursued both in animal models and in humans. They have also led to reassessment of the goals of vaccination. Necessity has sparked several creative new vaccine approaches involving nucleic acid or live attenuated viruses and vectors. With improved concepts of protective immune responses has come fervent discussion of the means to stimulate and maintain cell-mediated immunity. The result of this work is likely to be a more thorough understanding of antiviral immunity in the genital mucosa and the nervous system, and of HSV pathogenesis and immune evasion strategies, as additional strides are taken toward the goal of a successful vaccine with which to confront HSV.