GENETIC AND FUNCTIONAL APPRAOCH TO PREVENT VZV-INDUCED VASCULOPATHY

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

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. Primary infection with VZV results in varicella more commonly known as chickenpox. Interestingly, varicella is an important risk factor for childhood arterial ischemic stroke (AIS), accounting for a third of pediatric AIS cases. The reactivation of latent VZV during states of immune suppression results in a painful vesiculobullous eruption referred to herpes zoster (HZ, shingles). One of the most severe complications following VZV reactivation is vascular injury in the brain. VZV- related vasculopathy is particularly debilitating in the elderly and AIDS patients in whom it results in stroke and can lead to blindness or permanent neurological damage. Moreover, VZV-associated vascular diseases are difficult to diagnose and treatment options are limited to supportive care, antiviral and anticoagulant therapy. We believe that prevention of varicella and VZV reactivation through vaccination would reduce the frequency and severity of vascular complications, but the current VZV vaccines are not completely preventive. To design better vaccines to prevent VZV reactivation, we need to identify immunodominant genes and characterize protective immune responses. We will utilize a novel animal model in which nonhuman primates (NHP) infected with the highly homologous Simian varicella virus (SVV) will be used to identify immunogenic viral genes. Considerable molecular similarities between SVV and VZV, in addition to comparable clinical manifestations, indicate that SVV infection of NHP is a powerful animal model to study VZV pathogenesis. Our central hypothesis is that subunit vaccines expressing immunodominant VZV genes will boost pre-existing immunity to VZV and protect against vasculopathy associated with VZV reactivation.