Intranasal immunization with novel EspA-Tir-M fusion protein induces protective immunity against enterohemorrhagic Escherichia coli O157:H7 challenge in mice.
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome in humans. Due to the risks associated with antibiotic treatment against EHEC O157:H7 infection, vaccines represent a promising method for prevention of EHEC O157:H7 infection. Therefore, we constructed the novel bivalent antigen EspA-Tir-M as a candidate EHEC O157:H7 subunit vaccine. We then evaluated the immunogenicity of this novel EHEC O157:H7 subunit vaccine. Immune responses to the fusion protein administered by intranasal and subcutaneous routes were compared in mice. Results showed higher levels of specific mucosal and systemic antibody responses induced by intranasal as compared to subcutaneous immunization. Intranasal immunization enhanced the concentration of interleukin-4, interleukin-10, and interferon-γ, while subcutaneous immunization enhanced only the latter two. In addition, intranasal immunization protected against EHEC O157:H7 colonization and infection in mice at a rate of 90%.Histopathological analysis revealed that vaccination reduced colon damage, especially when administered intranasally. In contrast, subcutaneous immunization elicited a weak immune response and exhibited a low protection rate. These findings demonstrate that intranasal immunization with the fusion protein induces both humoral and cellular immune (Th1/Th2) responses in mice. The novel EspA-Tir-M novel fusion protein therefore represents a promising subunit vaccine against EHEC O157:H7 infection.
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Ruqin
R
Lin
Guangdong Provincial Key Laboratory of Gastroenterology, Inst. of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Bo
B
Zhu
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Yiduo
Y
Zhang
Guangdong Provincial Key Laboratory of Gastroenterology, Inst. of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Yang
Y
Bai
Guangdong Provincial Key Laboratory of Gastroenterology, Inst. of Gastroenterology of Guangdong Province, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Fachao
F
Zhi
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Beiguo
B
Long
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Yawen
Y
Li
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Yuhua
Y
Wu
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address: wxb70@126.com.
Xianbo
X
Wu
Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China. Electronic address: biofhy@126.com.
Hongying
H
Fan
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D003092:Colitis / Q000382:microbiology / Q000517:prevention & control; D003106:Colon / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000382:microbiology / Q000517:prevention & control*; D019453:Escherichia coli O157 / Q000276:immunology*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal; D007279:Injections, Subcutaneous; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D016207:Cytokines; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C102051:EspA protein, E coli; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C109287:Tir protein, E coli; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
Enterohemorrhagic Escherichia coli; Fusion protein; Immunogenicity; Subunit vaccine