中文摘要：本研究通过采用以Q19A或R140A为佐剂的单剂量新城疫（NDV）疫苗进行鼻内免疫分析了鸡IL--1β突变子Q19A或R140A作为粘膜免疫佐剂的潜力。与单独使用NDV疫苗或以Ch IL-113佐剂的NDV疫苗相比，采用Q19A或R140A作为佐剂能够显著提高血清血凝抑制抗体滴度以及免疫一周后抗NDV-特异性IgA抗体浓度，以及脾细胞干扰素-γ分泌水平；提高鼻组织中分泌的IgA水平。此外，将R140A与其受体（IL-1RI）和受体辅助蛋白（IL-1RAcP）结合进行分子动力学分析的结果表明：类野生型三元配合物降低了能量，从而促进R140A/IL-1RI/IL-1RAcP化合物的稳定性。总而言之，将Q19A 或R140A与NDV疫苗联合免疫，能够有效提高和增强鸡的粘膜免疫。
 
外文摘要：The use of cytokines as adjuvants in poultry is promising because they may enhance immune responses to antigens. In this study, we created two mutants, chicken interleukin-1 beta (ChIL-1 beta) Q19A and R140A, which exhibited significantly increased in vivo biological activity compared with wild-type ChIL-1 beta. The potential mucosal adjuvant activity of the mutants Q19A and R140A was evaluated in chickens through the intranasal coadministration of a single dose of the Newcastle disease virus (NDV) vaccine with Q19A or R140A. Compared with chickens vaccinated with only the NDV vaccine or the NDV vaccine plus wild-type recombinant ChIL-113, chickens vaccinated with Q19A or R140A had significantly increased serum hemagglutination-inhibition antibody titers and anti-NDV-specific IgA antibody levels 1 week later, a high amount of interferon-y secretion from splenocytes, and increased secretory IgA accumulated in nasal tissues. In addition, molecular dynamics simulations of the mutant R140A bound to its receptor (IL-1RI) and receptor accessory protein (IL-1RAcP) were more energetically favorable than the analogous wild-type ternary complex resulting in a decreased energy, which may stabilize the R140A/IL-1RI/IL-1RAcP complex. In conclusion, the mutants Q19A and R140A are effective adjuvants that accelerate and enhance chicken mucosal immunity when co-administered with one dose of the NDV vaccine.
外文关键词： Interleukin-1 beta； Molecular dynamics simulations； Mucosal immunity； Vaccine adjuvant
作者：Chen, WT; Chang, HK; Lin, CC; Yang, SM; Yin, HS
作者单位：台湾清华大学
期刊名称：MOLECULAR IMMUNOLOGY
期刊影响因子：3.236
出版年份：2017
出版刊次：7
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