Chicken interleukin-1β mutants are effective single-dose vaccine adjuvants that enhance mucosal immune response

被引:7
作者
Chen, Wen-Ting [1 ,2 ]
Chang, Hao-Kai [3 ]
Lin, Cheng-Chung [3 ]
Yang, Shan-Min [1 ,2 ]
Yin, Hsien-Sheng [1 ,2 ]
机构
[1] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, 101,Sect 2,Kuang Fu Rd, Hsinchu 30013, Taiwan
[2] Natl Tsing Hua Univ, Coll Life Sci, 101,Sect 2,Kuang Fu Rd, Hsinchu 30013, Taiwan
[3] Natl Chung Hsing Univ, Grad Inst Vet Pathobiol, 145 Xing Da Rd, Taichung 402, Taiwan
关键词
Interleukin-1; beta; Molecular dynamics simulations; Mucosal immunity; Vaccine adjuvant; RECOMBINANT OVINE IL-1-BETA; CRYSTAL-STRUCTURE; IFN-GAMMA; CYTOKINES; PROTEIN; ALPHA;
D O I
10.1016/j.molimm.2017.05.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:308 / 316
页数:9
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