Murine immunization with CS21 pili or LngA major subunit of enterotoxigenic Escherichia coli (ETEC) elicits systemic and mucosal immune responses and inhibits ETEC gut colonization.

Murine immunization with CS21 pili or LngA major subunit of enterotoxigenic Escherichia coli (ETEC) elicits systemic and mucosal immune responses and inhibits ETEC gut colonization.
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使用产肠毒素大肠杆菌 (ETEC) 的 CS21 pili 或 LngA 主要亚基对小鼠进行免疫接种,可引发全身和粘膜免疫反应,并抑制 ETEC 肠道定植。

DOI:
10.1016/j.vetmic.2016.02.001
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发表时间:
2017-04
影响因子:
3.3
通讯作者:
Gómez-Duarte OG
Gómez-Duarte OG
中科院分区:
农林科学2区
文献类型:
--
作者:
Zhang C;Iqbal J;Gómez-Duarte OG

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产肠毒素大肠埃希菌(ETEC)CS21菌毛是ETEC最常见的定植因子之一。CS21主要亚基LNGA介导ETEC与肠道细胞的黏附,并在ETEC新生小鼠感染模型中参与ETEC的发病。本工作的目的是评价LNGA主要亚基纯化蛋白和CS21纯化菌毛的免疫原性和对ETEC在小鼠肠道定植的保护作用。从E9034A ETEC株纯化的重组LngA蛋白或纯化的CS21菌毛免疫C57BL/6小鼠,检测其免疫原性。用ELISA法从小鼠血清、粪便和肠液中检测到特异性的抗LngA抗体。用野生型E9034A ETEC株口服免疫小鼠,通过随后从粪便中回收的细菌集落形成单位(CFU)的定量来评估对肠道定植的保护作用。重组LngA蛋白和CS21菌毛在小鼠模型中诱导产生特异性体液和粘膜抗LngA抗体。CS21联合CT鼻腔给药和LNGA联合不完全弗氏佐剂给药抑制ETEC在小鼠模型中的肠道定植。综上所述,ETEC的LngA纯化蛋白和CS21菌毛均具有较强的免疫原性,可抑制ETEC的肠道脱落。我们的免疫原性和免疫保护数据表明,CS21是未来ETEC腹泻多价疫苗的合适候选疫苗。
CS21 pili of enterotoxigenic Escherichia coli (ETEC) is one of the most prevalent ETEC colonization factors. CS21 major subunit, LngA, mediates ETEC adherence to intestinal cells, and contributes to ETEC pathogenesis in a neonatal mouse infection model. The objectives of this work were to evaluate LngA major subunit purified protein and CS21 purified pili on immunogenicity and protection against ETEC colonization of mice intestine. Recombinant LngA purified protein or purified CS21 pili from E9034A ETEC strain were evaluated for immunogenicity after immunization of C57BL/6 mice. Specific anti-LngA antibodies were detected from mice serum, feces, and intestine fluid samples by ELISA assays. Protection against gut colonization was evaluated on immunized mice orally challenged with wild type E9034A ETEC strain and by subsequent quantification of bacterial colony forming units (CFU) recovered from feces. Recombinant LngA protein and CS21 pili induced specific humoral and mucosal anti-LngA antibodies in the mouse model. CS21 combined with CT delivered intranasally as well as LngA combined with incomplete Freund adjuvant delivered intraperitoneally inhibited ETEC gut colonization in a mouse model. In conclusion, both LngA purified protein and CS21 pili from ETEC are highly immunogenic and may inhibit ETEC intestinal shedding. Our data on immunogenicity and immunoprotection indicates that CS21 is a suitable vaccine candidate for a future multivalent vaccine against ETEC diarrhea.