Enhanced immunogenicity of a novel Stx2Am-Stx1B fusion protein in a mice model of enterohemorrhagic Escherichia coli O157:H7 infection.
Shiga toxins (Stxs) which include Stx1 and Stx2 produced by EHEC O157:H7 are responsible for severe diseases, including hemolytic uremic syndrome (HUS) in humans. In our previous study, a fusion protein Stx2B-Stx1B (2S for short) was prepared and displayed immunogenicity against low lethal dose challenge of E. coli O157:H7. To enhance the immunogenicity against both toxins above, we constructed a novel fusion protein carrying the Stx1B subunit and enzyme-inactive Stx2A subunit, designated Stx2Am-Stx1B (SAmB for short). The fusion protein SAmB elicited high level humoral IgG and IgG1 in mice and induced Th2-typical cytokines IL-4/IL-10 but not Th1-typical cytokine INF-γ, indicating a partial to humoral immunoresponse mediated by Th2-type cells that contributed to this humoral reactivity. Higher level neutralizing antibodies against Stx2 were elicited by SAmB than 2S. An enhanced effect of protection (93.3%) against high lethal dose challenge of lysed E. coli O157:H7 was observed, and the SAmB also provided cross protection against purified Stx1 and Stx2.
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, PR China.
Kun
K
Cai
Xiang
X
Gao
Tao
T
Li
Qin
Q
Wang
Xiaojun
X
Hou
Wei
W
Tu
Le
L
Xiao
Maoren
M
Tian
Yuenan
Y
Liu
Hui
H
Wang
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing; D004927:Escherichia coli Infections / Q000382:microbiology / Q000517:prevention & control*; D019453:Escherichia coli O157 / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D022622:Shiga Toxin 1 / Q000235:genetics / Q000276:immunology*; D022641:Shiga Toxin 2 / Q000235:genetics / Q000276:immunology*
D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma