Antibody induction in mice by liposome-displayed recombinant enterotoxigenic Escherichia coli (ETEC) colonization antigens

IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomedical Journal Pub Date : 2023-12-01 DOI:10.1016/j.bj.2023.03.001
Shiqi Zhou , Karl O.A. Yu , Moustafa T. Mabrouk , Dushyant Jahagirdar , Wei-Chiao Huang , Julio A. Guerra , Xuedan He , Joaquin Ortega , Steven T. Poole , Eric R. Hall , Oscar G. Gomez-Duarte , Milton Maciel Jr. , Jonathan F. Lovell
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引用次数: 3

Abstract

Background

Enterotoxigenic Escherichia coli (ETEC) strains cause infectious diarrhea and colonize host intestine epithelia via surface-expressed colonization factors. Colonization factor antigen I (CFA/I), a prevalent ETEC colonization factor, is a vaccine target since antibodies directed to this fimbria can block ETEC adherence and prevent diarrhea.

Methods

Two recombinant antigens derived from CFA/I were investigated with a vaccine adjuvant system that displays soluble antigens on the surface of immunogenic liposomes. The first antigen, CfaEB, is a chimeric fusion protein comprising the minor (CfaE) and major (CfaB) subunits of CFA/I. The second, CfaEad, is the adhesin domain of CfaE.

Results

Owing to their His-tag, recombinant CfaEB and CfaEad, spontaneously bound upon admixture with nanoliposomes containing cobalt-porphyrin phospholipid (CoPoP), as well as a synthetic monophosphoryl lipid A (PHAD) adjuvant. Intramuscular immunization of mice with sub-microgram doses CfaEB or CfaEad admixed with CoPoP/PHAD liposomes elicited serum IgG and intestinal IgA antibodies. The smaller CfaEad antigen benefitted more from liposome display. Serum and intestine antibodies from mice immunized with liposome-displayed CfaEB or CfaEad recognized native CFA/I fimbria as evidenced by immunofluorescence and hemagglutination inhibition assays using the CFA/I-expressing H10407 ETEC strain.

Conclusion

These data show that colonization factor-derived recombinant ETEC antigens exhibit immunogenicity when delivered in immunogenic particle-based formulations.

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脂质体显示的重组产肠毒素大肠杆菌(ETEC)定殖抗原诱导小鼠抗体。
背景:产肠毒素大肠杆菌(ETEC)菌株引起感染性腹泻,并通过表面表达的定植因子定植宿主肠上皮。定植因子抗原I (CFA/I)是一种流行的ETEC定植因子,是一种疫苗靶点,因为针对该菌毛的抗体可以阻断ETEC粘附并预防腹泻。方法:用免疫原性脂质体表面显示可溶性抗原的疫苗佐剂系统研究了来自CFA/I的两种重组抗原。第一个抗原CfaEB是一个嵌合融合蛋白,包含CFA/I的次要亚基(CfaE)和主要亚基(CfaB)。第二个是CfaEad,是CfaE的粘附结构域。结果:重组CfaEB和CfaEad由于具有His-tag,可以与含有钴卟啉磷脂(CoPoP)的纳米脂质体以及合成的单磷酰脂质a (PHAD)佐剂自发结合。亚微克剂量CfaEB或CfaEad与CoPoP/PHAD脂质体混合肌肉免疫小鼠,可诱导血清IgG和肠道IgA抗体。较小的CfaEad抗原从脂质体展示中获益更多。使用表达CFA/I的H10407 ETEC菌株进行免疫荧光和血凝抑制实验证明,用脂质体免疫小鼠的血清和肠道抗体显示CfaEB或CfaEad可识别天然CFA/I纤维。结论:这些数据表明,定殖因子衍生的重组ETEC抗原在免疫原性颗粒配方中表现出免疫原性。
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来源期刊
Biomedical Journal
Biomedical Journal Medicine-General Medicine
CiteScore
11.60
自引率
1.80%
发文量
128
审稿时长
42 days
期刊介绍: Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs. Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology. A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.
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