Vaccine against cholera and enterotoxigenic E. coli (ETEC) diarrhea
Inventors
Holmgren, Jan • Lebens, Michael
Assignees
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Publication Number
US-9511133-B2
Publication Date
2016-12-06
Expiration Date
Abstract
A vaccine against cholera and/or ETEC is provided, comprising a Vibrio cholerae O1 cell, characterized in that said cell comprises O1 antigens of both Ogawa and lnaba serotypes. Genetically modified Vibrio cholerae O1 cells for use in such vaccines, DNA-constructs for the modification, uses for the vaccine and methods of making a vaccine are also provided.
Core Innovation
The invention provides a vaccine comprising multiple formalin inactivated Vibrio cholerae O1 cells that simultaneously express O1 antigens of both Ogawa and Inaba serotypes. The cells are characterized in that between 10-90% of the O1 antigens expressed by the cells are of the Ogawa-serotype.
The invention further specifies control of O1 serotype antigen expression using the endogenous wbeT gene and WbeT enzyme activity. The endogenous wbeT gene of the producing cell, or the protein coded thereof, is inactive, and a recombinant DNA-construct is provided that expresses a WbeT enzyme having WbeT enzyme activity at a level that enables simultaneous expression of Inaba and Ogawa antigens.
The recombinant WbeT protein comprises at least 99% sequence identity to SEQ ID NO: 6 and includes a substitution of the serine residue in position 158 of SEQ ID No: 6. The engineered approach is described as enabling an engineered O1 cell that supports simultaneous Inaba and Ogawa antigen expression, including a Hikojima-like phenotype.
In addition to the O1 antigen system, the vaccine may further include expression of enterotoxigenic E. coli (ETEC) colonization factor proteins, such as CFA/I, CS2, and CS5, including hybrid fimbriae. The use case is a preventive immunization, with oral administration mentioned in the document and formulation described for oral use.
Claims Coverage
The document provides at least two independent claim scopes: a vaccine composition and an engineered Vibrio cholerae O1 cell. Across these scopes, the main inventive features are controlled simultaneous Ogawa and Inaba O1 antigen expression in formalin inactivated material, achieved by inactivating endogenous wbeT and expressing a recombinant WbeT enzyme/protein with defined sequence identity and a serine-158 substitution to set the Ogawa:Inaba antigen balance (10-90% Ogawa).
Formalin inactivated vaccine with simultaneous Ogawa and Inaba O1 antigens at 10-90% Ogawa
A vaccine comprising multiple Vibrio cholerae O1 cells that simultaneously express O1 antigens of both Ogawa and Inaba serotypes, wherein between 10-90% of the O1 antigens expressed by the cells are of the Ogawa-serotype, and wherein the cells are formalin inactivated.
Engineered Vibrio cholerae O1 cell with inactive endogenous wbeT and recombinant WbeT activity for simultaneous Inaba and Ogawa antigens
A Vibrio cholerae O1 cell simultaneously expressing both Inaba and Ogawa antigens, wherein the endogenous wbeT-gene of the cell or the protein coded thereof is inactive; the cell comprises a recombinant DNA-construct expressing a WbeT enzyme having WbeT enzyme activity; and wherein the level of the WbeT enzyme activity of the WbeT enzyme expressed is such that the cell simultaneously expresses Inaba and Ogawa antigens.
Recombinant WbeT protein defined by SEQ ID NO: 6 identity and serine residue substitution at position 158
The cell comprises a recombinant Wbe T-protein having at least 99% sequence identity to SEQ ID NO: 6 and comprising a substitution of the serine residue in position 158 of SEQ ID No: 6.
Overall, claim coverage centers on formalin inactivated Vibrio cholerae O1 vaccine material and engineered Vibrio cholerae O1 cells that simultaneously express Ogawa and Inaba O1 antigens, with endogenous wbeT inactivation, recombinant WbeT activity, a 10-90% Ogawa fraction, and a recombinant WbeT protein defined by at least 99% sequence identity to SEQ ID NO: 6 with a serine-158 substitution.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Preventive immunization with oral administration [procedural detail omitted for safety].
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