Chiang Chen-Yi, Liu Shih-Jen, Hsieh Chun-Hsiang, Chen Mei-Yu, Tsai Jy-Ping, Liu Hsueh-Hung, Chen I-Hua, Chong Pele, Leng Chih-Hsiang, Chen Hsin-Wei
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan.
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
Vaccine. 2016 Feb 17;34(8):1054-61. doi: 10.1016/j.vaccine.2016.01.009. Epub 2016 Jan 15.
The linkage of an immunogen with a toll-like receptor ligand has great potential to induce highly potent immune responses with the initial features of antigen-presenting cell activation. In the current study, we expressed recombinant dengue-3 envelope protein domain III (D3ED III) in lipidated form using an Escherichia coli-based system. The recombinant lipidated dengue-3 envelope protein domain III (LD3ED III) augments the expression levels of IL-12 family cytokines. LD3ED III-immunized mice enhance wide ranges of T cell responses as indicated by IFN-γ, IL-17, IL-21 production. Additionally, LD3ED III-immunized mice increase the frequencies of anti-D3ED III antibody producing cells. The boosted antibody titers cover various IgG isotypes, including IgG1, IgG2a, IgG2b, and IgG3. Importantly, LD3ED III-immunized mice induce neutralizing antibody capacity associated with a reduction of viremia levels after challenges. In contrast, mice that are immunized with D3ED III formulated with aluminum phosphate (D3ED III/Alum) only enhance Th2 responses and boost IgG1 antibody titers. Neither neutralizing antibody responses nor the inhibition of viremia levels after challenge is observed in mice that are immunized with D3ED III/Alum. These results suggest that LD3ED III can induce broad profiles of cellular and humoral immune responses.
免疫原与Toll样受体配体的连接具有极大潜力，可诱导出具有抗原呈递细胞激活初始特征的高效免疫反应。在本研究中，我们使用基于大肠杆菌的系统表达了脂化形式的重组登革热3型包膜蛋白结构域III（D3ED III）。重组脂化登革热3型包膜蛋白结构域III（LD3ED III）可提高IL-12家族细胞因子的表达水平。如IFN-γ、IL-17、IL-21的产生所示，用LD3ED III免疫的小鼠增强了广泛的T细胞反应。此外，用LD3ED III免疫的小鼠增加了产生抗D3ED III抗体细胞的频率。增强的抗体滴度涵盖了各种IgG亚型，包括IgG1、IgG2a、IgG2b和IgG3。重要的是，用LD3ED III免疫的小鼠诱导出中和抗体能力，且在攻毒后病毒血症水平降低。相比之下，仅用磷酸铝配制的D3ED III免疫的小鼠（D3ED III/明矾）仅增强Th2反应并提高IgG1抗体滴度。在用D3ED III/明矾免疫的小鼠中未观察到中和抗体反应或攻毒后病毒血症水平的抑制。这些结果表明，LD3ED III可诱导广泛的细胞免疫和体液免疫反应。
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