Chih-Chun Wen,1,2 Pen-Wen Hsiao,1 Yi-Chun Yeh,1 Sheng-Chu Kuo,2 Li-Jiau Huang,2 Aravindaram Kandan,1 Ning-Sun Yang,1
1Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan; 2Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan.
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 important to develop an effective vaccine to prevent possible recurrence of a SARS epidemic. 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 (SARS-CoVLPs) and DCs as an initiation step of the immune response. Co-culturing of SARS-CoVLPs with DC at different time points in primary culture induced phenotypic maturation of human monocyte-derived DCs. Through ELISA, we also observed increased levels on the expressions of proinflammatory cytokines (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 of SARS-CoVLPs as an immunogen. SARS-CoVLPs and SAR-CoVLP-based DNA vaccine were either injected subcutancously 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 increased significantly after priming, boosting and a second boosting. We also observed an increased IFN-g production from splenocytes of vaccinated mice, as measured by ELISPOT assay. Taken these data together, our results indicated that the SARS-CoVLPs we developed can further induce a Th1-biased immune response and may represent a promising approach for SARS vaccine development.