DEVELOPMENT OF A NONHUMAN PRIMATE MODEL FOR VARICELLA AND HERPES ZOSTER

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since the life span of the world population is increasing, health complications as a result of immune senescence will undoubtedly increase as well. Amongst these complications is herpes zoster (shingles) caused by the reactivation of Varicella Zoster Virus. The currently approved zoster vaccine (ZosterVax from Merck) reduces the incidence of herpes zoster by 50%. Therefore, 50% of this population remains susceptible to zoster and its ensuing neurological complications. Studies to improve the efficacy and safety of this vaccine require an improved understanding of the immune response to VZV during different stages of the disease. However, these studies are complicated since an experimental animal model that can recapitulate both the acute (varicella, chickenpox) and reactivation (zoster) forms of the disease is currently not available. An alternative is to utilize a nonhuman primate (NHP) model that is susceptible to infection by the closely related virus Simian varicella virus (SVV). Indeed, considerable clinical and molecular similarities between SVV and VZV indicate that SVV infection of NHP has considerable potential as an animal model. We have recently shown that infection of rhesus macaques with SVV recapitulates the hallmarks of VZV infection in humans including: the development of varicella rash, humoral and cellular immunity, resolution of acute viremia and the establishment of latency in sensory ganglia. This novel model will allow a deeper understanding of the immune deficiencies that underlie VZV reactivation in elderly subjects, which in turn will facilitate the design of efficacious vaccines to boost specific aspects of VZV immune surveillance.