Adhesin as immunogen against enterotoxigenic Escherichia coli
AssigneeThe United States of America as represented by the Secretary of the Navy
InventorStephen J. Savarino
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Abstract
The inventive subject matter relates to the methods for the induction of immunity and prevention of diarrhea resulting from Escherichia coli. The inventive subject matter also relates to the use Escherichia coli adhesins as immunogens and to the construction of conformationally stability and protease resistant Escherichia coli adhesin constructs useful for inducing immunity to Escherichia coli pathogenic bacteria. The methods provide for the induction of B-cell mediated immunity and for the induction of antibody capable of inhibiting the adherence and colonization of Escherichia coli, including enterotoxigenic Escherichia coli, to human cells.
Claims21
A method of inducing an immune response against enterotoxigenic Escherichia coli comprising the steps:
- a. administering a priming dose of an immunogen comprising whole or a polypeptide fragment of enterotoxigenic Escherichia coli fimbriae or whole or a polypeptide fragment of enterotoxigenic Escherichia coli fibrillae, with a unit dose range of said priming dose of 50 μg to 1 mg of said immunogen;
- and
- b. administering boosting doses of said immunogen, with a first dose administered at least 1 week after said priming dose, with a unit dose range of said boosting doses of 50 μg to 1 mg of said immunogen, whereby an immune response is elicited;
- wherein said immunogens are conformationally stable variants engineered using in cis donor strand complementation;
- wherein said whole or a polypeptide fragment of enterotoxigenic Escherichia coli fimbriae are conformationally-stable Escherichia coli fimbrial adhesin polypeptide constructs comprising a major structural fimbrial subunit;
- and wherein said whole or a polypeptide fragment of ore-said enterotoxigenic Escherichia coli fibrillae are conformationally-stable CstH constructs.
Dependencies are inferred from the claim text.