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表达巨型艾美耳球虫原肌球蛋白的转基因柔嫩艾美耳球虫引发增强的保护性免疫并改变鸡的肠道微生物组。

Transgenic Eimeria tenella Expressing Profilin of Eimeria maxima Elicits Enhanced Protective Immunity and Alters Gut Microbiome of Chickens.

机构信息

State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China.

State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing, China

出版信息

Infect Immun. 2018 Aug 22;86(9). doi: 10.1128/IAI.00888-17. Print 2018 Sep.

Abstract

Coccidiosis is one of the most serious diseases of livestock and birds in the world. Vaccination with live-parasite anticoccidial vaccines with genetic manipulation improving the immunogenicity of vaccine strains would be the best means for controlling coccidiosis in breeder and layer stocks, even in fast-growing broilers. Profilin from apicomplexan parasites is the first molecularly defined ligand for Toll-like receptor 11 (TLR11) and TLR12 in mice and is a potential molecular adjuvant. Here, we constructed a transgenic line (Et-EmPro) expressing the profilin of , the most immunogenic species of chicken coccidia, and evaluated the adjuvant effects of EmPro on the immunogenicity of We found that immunization with the transgenic parasites, compared with the wild type, elicited greater parasite antigen-specific cell-mediated immunity, characterized by increased numbers of interferon gamma (IFN-γ)-secreting lymphocytes. The transgenic parasite also induced better protective immunity against challenge than the wild type. In addition, the diversity of the fecal microbiome of the birds immunized with the transgenic parasite differed from that of the microbiome of the wild-type-immunized birds, indicating interactions of with the gut microbiome of chickens. Our results showing enhanced immunogenicity of by use of EmPro as a molecular adjuvant derived from the most immunogenic affinis species represent a large step forward in the development of the next generation of coccidiosis vaccines using as a vaccine platform expressing molecular adjuvants and potentially other pathogen antigens against not only coccidiosis but also other infectious diseases.

摘要

球虫病是世界上家畜和家禽最严重的疾病之一。用具有遗传改造的活寄生虫抗球虫疫苗进行免疫接种,提高疫苗株的免疫原性,将是控制种鸡和蛋鸡球虫病的最佳方法,即使在快速生长的肉鸡中也是如此。锥虫寄生虫的原肌球蛋白是小鼠中 Toll 样受体 11(TLR11)和 TLR12 的第一个分子定义配体,是一种有潜力的分子佐剂。在这里,我们构建了一个表达鸡球虫最具免疫原性种的原肌球蛋白的转基因系(Et-EmPro),并评估了 EmPro 对的免疫原性的佐剂作用。我们发现,与野生型相比,用转基因寄生虫免疫可引起更强的寄生虫抗原特异性细胞介导免疫,表现为干扰素γ(IFN-γ)分泌淋巴细胞数量增加。转基因寄生虫还诱导了比野生型更好的针对的保护性免疫。此外,用转基因寄生虫免疫的鸟类的粪便微生物组的多样性与用野生型免疫的鸟类的微生物组不同,表明与鸡的肠道微生物组相互作用。我们的结果表明,使用源自最具免疫原性亲缘种的 EmPro 作为分子佐剂,可增强的免疫原性,这代表了使用作为表达分子佐剂和潜在其他病原体抗原的疫苗平台开发下一代球虫病疫苗的一大进步,不仅针对球虫病,而且针对其他传染病。

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