Development and Utilization of Novel Immunologic Reagents for Infectious Disease Studies in the Guinea Pig

Genital herpes disease caused by HSV-2 infections is a worldwide public health epidemic with a global prevalence estimated at 500 million. These individuals serve as a reservoir for transmission of the virus to naïve individuals resulting in a global increase of 26 million new infections per year. Complications associated with first-episode infections acquired from horizontal transmission can include aseptic meningitis and psychosocial morbidity and neonates can be infected by virus shed into the vagina during birth leading to the development of severe sequelae or even death. Infection with HSV-2 also increases the susceptibility to HIV-1 infection more than five-fold. Antiviral chemoprophylaxis exists capable of reducing or abrogating clinical signs of primary or recurrent disease outbreaks, however long-term antiviral suppression does not clear the latent infection and cannot completely prevent transmission to the uninfected. There is currently no licensed vaccine to prevent HSV-2 infection and failures in recent clinical trials highlight the need for improved vaccine formulations containing multiple antigenic targets in order to stimulate a robust humoral and cellular immune response. The most widely used animal model for the study of genital herpes is the mouse, however studies in this animal are limited to acute infection only. The guinea pig, a more robust model that closely mimics human disease, can be used to study both primary and recurrent disease, however this animal model is limited due to the lack of immune reagents for this species. Development of new reagents to elucidate the immune response to infection and disease in the guinea pig would therefore benefit the field of genital herpes and other diseases for which the guinea pig is the better animal model.