DETERMINATION OF IMMUNE CORRELATES OF PROTECTION FOR CHIKV INFECTIONS

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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. Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for recent outbreaks in and around the Indian Ocean. To date, infections have been limited to Africa and the Indian Ocean Region; however, spread to the Southeastern US is possible. CHIKV-induced arthritis mainly of the joints and wrists can be extremely debilitating and can last for weeks to years. Severe cases involving infections of the central nervous system have been described in neonates and predisposed adults with underlying conditions and over 200 fatalities (1%) were associated with the disease on the French island of Reunion in 2005-6. The pathophysiology of CHIKV infection, immune correlates of protection and the basis for disease severity are poorly understood. To address these critical issues, we will develop a NHP model of CHIKV infection in rhesus macaques (RM) to be used for therapy and vaccine studies. First, we will determine the natural progression of CHIKV disease and the immunological parameters associated with viral infection in RM. We will also test whether aged RM are more susceptible to develop chronic CHIKV disease than adult RM as this anecdotally seems to be the case for human disease. Then we will determine the correlates of immune protection to CHIKV infection and disease in adult and aged RM by depleting crucial subsets of immune cells (CD4 or CD8 T cells or B cells) or by the passive transfer of convalescence serum isolated from infected animals and then following virus dissemination and disease parameters.