154. Severe Acute Respiratory Syndrome Coronavirus-Like Particles (SARS-CoVLPs) Stimulate Human Monocyte-Derived Dendritic Cell Activity and Induce Antibody Response in Mouse Model
Severe acute respiratory syndrome (SARS) is a life-threatening disease caused by a novel SARS associated coronavirus (SARS-CoV). For public health measures, it is very importantto develop an effectivevaccineto preventpossiblerecurrenceofa SARSepidemic. Dendritic cells (DCs) have been recognized as potent antigen presenting cells and the key regulators of innate and adaptive immune responses. In this investigation, we have studied the interaction between SARS-Co virus like particles
... ticles (SARS-CoVLPs) and DCs as an initiationstep of the immune response,Co-culturing ofSARS-CoVLPs with DC at differenttime points in primaryculture induced phenotypic maturation of human monocyte-derived DCs. Through ELISA, we also observed increased levelson the expressionsof proinflammatorycytokines (e.g., TNF-a and IL-6) in the cell culture of SARS-CoVLPs-pulsed DCs. Furthermore, SARS-CoVLPs-pusled DCs induced allogeneic CD4 and CD8 T cell proliferations and increased IFN-g secretion. We then further investigated the in vivo immune response on the use ofSARS-CoVLPs as an immunogen. SARS-CoVLPs and SAR-CoVLP-based DNA vaccine were either injected subcutaneously or delivered into skin of test mice via gene gun bombardment. The VLP-based ELISA indicated that IgG antibody responses to SARS-CoVLPs and SARS based DNA vaccine increasedsignificantly after priming,boostingand a secondboosting. Wealso observedan increasedIFN-gproductionfromsplenocytesof vaccinated mice, as measured by ELiSPOT assay.Taken these data together,our results indicatedthat the SARS-CoVLPswe developed can further inducea Th I-biased immuneresponseand may represent a promising approach for SARS vaccine development.