数字农科院2.0

Design and Evaluation of a Broadly Multivalent Adhesins-Based Multi-Epitope Fusion Antigen Vaccine Against Enterotoxigenic Escherichia coli Infection

文献类型： 外文期刊

作者： Yanyan Jia;Ke Yang;Qijuan Sun;Weiqi Guo;Zhihao Yang;Zihan Duan;Shiqu Zhang;Rongxian Guo;Ke Ding;Chengshui Liao;Shaohui Wang

作者机构：

关键词： enterotoxigenic Escherichia coli;fimbriae;immune efficacy;multi-epitope fusion antigen;multivalent vaccine

期刊名称： Vaccines

ISSN： 2076-393X

年卷期： 2025 年 13 卷 10 期

页码：

收录情况： SCIE（2025版）

摘要： Background: Enterotoxigenic Escherichia coli (ETEC) is a zoonotic pathogen causing diarrhea and mortality in infants and livestock. Its numerous serotypes necessitate the urgent development of multivalent vaccines for effective prevention, thereby reducing public health and economic threats. Methods: Computational bioinformatics analyses were conducted on five major ETEC adhesins structural subunits (FaeG, FanC, FasA, FimF41a, and FedF). Dominant epitopes were selected and concatenated via flexible linkers, incorporating the PADRE sequence and LTb adjuvant to design a multi-epitope fusion antigen (MEFA). The recombinant MEFA protein was expressed in a prokaryotic system. Furthermore, molecular dynamics simulations, docking, and immune simulations assessed structural stability and immunogenicity. Immunoreactivity was tested by Western blot. Murine immunization evaluated antibody responses, lymphocyte proliferation, cytokine secretion, and protection against ETEC challenge. Results: Structural modeling showed an extended conformation, with docking and simulations indicating strong immune activation. Western blot confirmed MEFA immunoreactivity. MEFA induced high antigen-specific antibody titers, enhanced splenocyte proliferation, and increased IFN-γ and IL-4 secretion, indicating a Th2-biased response in mice. Vaccinated mice survived lethal ETEC challenge and maintained intestinal integrity. Conclusions: The MEFA candidate vaccine effectively induces robust humoral and cellular immune responses and provides protection against ETEC infection, representing a promising strategy for next-generation multivalent ETEC vaccines.

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