POLY(I:C) PROTECTS NEONATAL MICE FROM SINDBIS VIRUS INFECTION
2Division of Biotechnology Review and Research-III, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland
Emerging pathogens with pandemic potential and lacking effective treatment or vaccines pose a major world-wide risk. Yet, developing, testing and licensing safe and effective vaccines or pathogen-specific drugs in a reasonable time frame are rarely feasible. Innate immune modulators have been proposed as alternative 1st response treatments. In these studies we explore their effectiveness using a novel model for Sindbis virus (SINV), developed in our lab, uses the wild type SINV strain AR339 in neonatal C57BL/6 mice. SINV is an alphavirus that causes sindbis fever in humans and serves as a prototype virus for other highly pathogenic alphaviruses such as Chikungunya, Semliki Forest and Venezuelan Equine viruses.
The aims of this study were to evaluate the effects of administration of double stranded RNA adjuvant poly(I:C) (5 mg/kg; i.p.) on the periphery and the central nervous system and to examine whether we can harness this response to reduce the severity of SINV infections. We show that systemic administration of poly(I:C) induced a broad spectrum of innate immune related genes both in the spleen and brain of naive immunocompetent mice. The shift in gene expression was associated with protection of SINV infected mice that received poly(I:C) one day prior to infection. Using IFNAR KO and RAG KO mice we demonstrate that protection is mediated by Type I IFN signaling but does not require adaptive immunity. This study suggest that innate immune response modifiers should be considered as a treatment modality for infections, to which, specific effective vaccine or therapy are not available.
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