title: Oral Immunization with RecombinantLactobacillus acidophilusExpressing espA-Tir-M Confers Protection against EnterohemorrhagicEscherichia coliO157:H7 Challenge in Mice.
abstract: EnterohemorrhagicEscherichia coliO157:H7 (EHEC O157:H7) causes hemorrhagic colitis and the formation of characteristic attaching and effacing (A/E) lesions in humans. Given the severe sequelae of EHEC O157:H7 infection, it is critical to develop effective vaccines for human use. However, for achieving this goal many hurdles need to be addressed, such as the type or subset of antigens, adjuvant, and the delivery route. We developed a candidate vaccine by inserting the bivalent antigen espA-Tir-M composed of espA and the Tir central domain intoLactobacillus acidophilus. The recombinantL. acidophilus(LA-ET) was safe in a cell model and excluded EHEC O157:H7 from LoVo cells at rates of nearly 94 and 60% in exclusion and competition assays, respectively. LA-ET inhibited the induction of A/E lesions by EHEC O157:H7 cellsin vitro. Oral immunization with LA-ET induced higher levels of specific mucosal and systemic antibody responses in mice. Moreover, LA-ET enhanced interferon-γ and interleukin-4 and -10 production, which was associated with mixed helper T (Th1/Th2) cell responses, and protected against EHEC O157:H7 colonization and infection in mice at a rate of 80%. Histopathological analyses revealed that orally administered LA-ET reduced or inhibited A/E lesions and toxin-induced systemic injury. These findings demonstrate that LA-ET induces both humoral and cellular immune responses in mice and is therefore a promising vaccine against EHEC O157:H7 infection.
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Ruqin
authors.initials: R
authors.lastname: Lin
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Yiduo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Beiguo
authors.initials: B
authors.lastname: Long
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Siqin
authors.initials: S
authors.lastname: Duan
authors.affiliation: The First School of Clinical Medicine, Southern Medical University Guangzhou, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Xianbo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University Guangzhou, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Fan
keywords: A/E lesions; Escherichia coli O157:H7; Lactobacillus acidophilus; live vector vaccine; probiotics