Alphavirus particle filovirus vaccine activation of Dendritic cells (52.7)

Abstract

Abstract Filoviruses, Marburg (MARV) and Ebola (EBOV), are among the deadliest etiological agents causing hemorrhagic fevers. Although little is known about the pathogenesis or what immunological responses are required to protect against filoviruses, a promising recombinant RNA replicon vaccine has been developed consisting of an attenuated alphavirus, Venezuelan equine encephalitis virus (VEE), to express MARV and EBOV viral genes such as the virus glycoprotein (GP). While numerous in vivo studies have demonstrated the protective efficacy of filovirus GP expressing VEE replicon particles (GP-VRP) in mice, guinea pigs, and non-human primates, when challenged with homologous virus, little has been done to understand the means by which these VRP filovirus vaccines initiate and establish immunity. In this study, we sought to dissect the protective mechanism of VRPs by evaluating the GP-VRPs effects on dendritic cells (DCs) by several characterization assays. Immunofluorescence assay (IFA), flow cytometry, and cytokine detection assays were used to assess maturation, co-stimulatory molecule expression, and cytokine expression profiles of GP-VRP-treated DCs. These findings will aid in deciphering early innate immune responses initiated by GP-VRP vaccination that are necessary for eliciting protective immunity against filovirus infection.