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经鼻递送含有肝片吸虫组织蛋白酶L5和组织蛋白酶B2阶段特异性重组蛋白的制剂可引发抗繁殖力效应,并通过佐剂介导减少绵羊体内吸虫负荷。

Intranasal delivery of a formulation containing stage-specific recombinant proteins of Fasciola hepatica cathepsin L5 and cathepsin B2 triggers an anti-fecundity effect and an adjuvant-mediated reduction in fluke burden in sheep.

作者信息

Norbury Luke J, Basałaj Katarzyna, Zawistowska-Deniziak Anna, Sielicka Alicja, Wilkowski Przemysław, Wesołowska Agnieszka, Smooker Peter M, Wędrychowicz Halina

机构信息

Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Twarda 51/55, 00-818 Warsaw, Poland; School of Science, Royal Melbourne Institute of Technology University, Bundoora, Victoria 3083, Australia.

Witold Stefański Institute of Parasitology, Polish Academy of Sciences, Twarda 51/55, 00-818 Warsaw, Poland.

出版信息

Vet Parasitol. 2018 Jul 15;258:14-23. doi: 10.1016/j.vetpar.2018.05.008. Epub 2018 Jun 9.

DOI:10.1016/j.vetpar.2018.05.008
PMID:30105973
Abstract

Fasciola hepatica infection continues to be a major problem in the agriculture sector, particularly in sheep and cattle. Cathepsin L and B proteases are major components of the excretory/secretory material of the parasite, and their roles in several important aspects of parasite invasion and survival has led to their use as targets in rational vaccine design. Previous studies in rats demonstrated that the use of stage-specific antigens, cathepsin B2 and cathepsin L5, as part of a multivalent vaccine, was able to confer significant protection against challenge. In the present study, recombinant versions of cathepsin L5 and cathepsin B2 produced in yeast were used in combination to vaccinate sheep. Intramuscular and intranasal forms of administration were applied, and sheep were subsequently challenged with 150 F. hepatica metacercariae. Intramuscular vaccination was able to induce a strong systemic antibody response against both antigens, but failed to confer significant protection. Conversely, no elevated antibody response was detected against the vaccine antigens following nasal vaccination; however, a reduction in parasite egg viability (>92%) and a statistically significant (p = 0.006), predominantly adjuvant-mediated reduction in worm burdens was observed.

摘要

肝片吸虫感染仍然是农业领域的一个主要问题,尤其是在绵羊和牛身上。组织蛋白酶L和B蛋白酶是该寄生虫排泄/分泌物质的主要成分,它们在寄生虫入侵和存活的几个重要方面所起的作用,使其成为合理疫苗设计的靶点。先前在大鼠身上进行的研究表明,使用阶段特异性抗原组织蛋白酶B2和组织蛋白酶L5作为多价疫苗的一部分,能够对攻击提供显著保护。在本研究中,将酵母中产生的组织蛋白酶L5和组织蛋白酶B2的重组形式联合用于给绵羊接种疫苗。采用肌肉注射和鼻内给药方式,随后用150只肝片吸虫囊蚴对绵羊进行攻击。肌肉注射疫苗能够诱导针对两种抗原的强烈全身抗体反应,但未能提供显著保护。相反,鼻内接种疫苗后未检测到针对疫苗抗原的抗体反应升高;然而,观察到寄生虫卵活力降低(>92%),并且在统计学上有显著意义(p = 0.006),主要是佐剂介导的蠕虫负荷降低。

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