title: Nanoparticulated heat-stable (STa) and heat-labile B subunit (LTB) recombinant toxin improves vaccine protection against enterotoxigenic Escherichia coli challenge in mouse.
abstract: Enterotoxigenic Escherichia coli (ETEC) remains a major cause of diarrheic disease in developing areas, for which there is no effective vaccine available. In this study, we genetically engineered a recombinant heat-stable enterotoxin (STa) coupled to the subunit B of heat-labile enterotoxin (LTB). This fusion protein, STa-LTB, possesses a single amino acid substitution at position 14 of STa. Our data demonstrates that the enterotoxicity of STa in STa-LTB was dramatically reduced. A gelatin nanovaccine candidate was prepared using the purified STa-LTB fusion protein characterized with an entrapment efficiency of 84.88 ± 6.37% and smooth spheres size ranges of 80-200 nm. Antigen-specific antibody responses against STa-LTB and STa in the sera and the intestinal mucus respectively were used to test the immunogenicity of the nanovaccine. This vaccine was further screened in mice by its ability to elicit neutralizing antibodies against STa and protect animals from the challenge with ETEC in mice. The STa-LTB nanoparticles delivered demonstrated a capacity to induce significantly higher and long-lasting antibody responses and increased immune protection against ETEC challenge relative to the control STa-LTB vaccine absorbed in conventional aluminum hydrate salt (p < 0.01). These results warrant the further studies of the development of a novel nanoparticulate vaccine as a broad-spectrum vaccine against ETEC infection.
authors.affiliation: Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, 539 W. Helanshan Road, Yinchuan, Ningxia 750021, PR China.
authors.forename: Guangcun
authors.initials: G
authors.lastname: Deng
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Minjie
authors.initials: M
authors.lastname: Jian
authors.forename: Wenmiao
authors.initials: W
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Yujiong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000276:immunology*; D054307:Enterotoxigenic Escherichia coli / Q000737:chemistry / Q000276:immunology*; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D005260:Female; D005780:Gelatin / Q000737:chemistry; D006358:Hot Temperature; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification
chemical_list: D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D005780:Gelatin