The development of DNA vaccine against H1N1 influenza virus in animal model

• Main Authors: Chia Yuan Chen, 陳嘉媛
• Other Authors: J. T. Qiu
• Format: Others
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/85300250679357506080

碩士 === 長庚大學 === 生物醫學研究所 === 102 === Influenza virus infection causes both epidemic and pandemic flu in humans and animals. DNA vaccines are a good strategy to induce immunity and prevent virus infection, because they can be produced rapidly and are relatively safe and stable. DNA vaccines have been highly effective in mice, but have shown limited efficiency in larger animals. This limitation can be overcome by enhancing the immunogenicity of DNA-based vaccines. In this study, we used codon optimization to increase protein expression and used mouse cytotoxic T-lymphocyte antigen 4 (mCTLA-4) as a modulatory adjuvant to bind directly to functional antigen-presenting cells (APC). Moreover, we compared the immunogenicity of two forms of hemagglutinin (HA) antigen, full-length and C-terminal deletion HA. We found that the codon-optimized HA gene (pcHA) could translate into a higher amount of protein possibly through increased mRNA levels. Besides, both cellular and humoral responses were enhanced by codon- optimization. In the cytokine secretion assay, all the plasmids used showed high interferon-γ (IFN-γ) production, especially the pCTLA4-cHA, and no significant differences were noted in the interleukin-4 (IL-4) secretion. pcHA-vaccinated mice induced the highest percentage of IFN-γ+ T-cells. These results indicate that codon-optimized HA could enhance vaccine potency whereas mCTLA-4-fused DNA vaccine had no significant response.