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3xSTaA14Q-LT(S63K/R192G/L211A) toxoid fusion for developing antitoxin vaccine against enterotoxigenic Escherichia coli associated diarrhea

技术优势

A fusion carrying three copies of a STa toxoid to enhance anti-STa immunity, and a triple mutant L T to further eliminate LT enterotoxicity, for safe vaccine development.

详细技术说明

The invention provides a fusion protein containing 3 copies of a STa mutant protein, as well as a triple mutant LT A1 fragment. This combination creates enhanced immunogenic response to STa as well as reducing the toxicity of the LT toxin. This can be applied to multiple vaccine delivery methods.

*Abstract

Diarrhea continues to be one of the most important diseases worldwide. It causes up to two millions of deaths annually to children under the age of five, more than AIDS, malaria and measles combined. Enterotoxigenic Escherichia coli (ETEC) strains are the major cause to children's diarrhea, and also travelersΓÇÖ diarrhea. Currently there are no vaccines available to protect against ETEC diarrhea. Pathogenesis of ETEC diarrhea hasbeen well studied. The virulence determinants are ETEC colonization factor antigen (CF A, and coli surface antigen - CS) adhesins and two enterotoxins (heat-labile toxin - LT, and heat-stable toxin - STa). CFA adhesins mediate bacteria attachment to host epithelial cells and facilitate bacteria colonization at host small intestines, but it is the LT and STa enterotoxins that disrupt fluid homeostasis in host epithelial cells to cause fluid hypersecretion that leads to diarrhea. Therefore, antitoxin vaccines to neutralize LT and STa toxins are essential to protection against ETEC-associated diarrhea.

国家/地区

美国