Targets of acinetobacter baumannii
Inventors
Urwyler, Simon • Haake, Markus • Rudolf, Michael
Assignees
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Publication Number
US-10463727-B2
Publication Date
2019-11-05
Expiration Date
Abstract
The present invention provides antigenic polypeptides expressed during an infection by a pathogenic organism, such as Acinetobacter and compositions comprising these polypeptides. The invention further provides compositions for use in treating, preventing or detecting a bacterial infection, in particular vaccine compositions using the antigenic polypeptides. The invention further provides antibodies directed to said antigenic polypeptides.
Core Innovation
The invention relates to immunogenic compositions for generating an immune response against Acinetobacter baumannii in a subject in need thereof, using isolated polypeptides and adjuvants. The platform identifies antigenic polypeptides expressed during infection and provides defined immunogenic polypeptide sequences including sequence identifiers and encoded polypeptides with immunostimulatory activity.
A recombinant nucleic acid sequence encoding a selected immunogenic polypeptide is used to produce an isolated polypeptide by expression in a host cell transformed/transfected with an expression vector, followed by purifying the polypeptide from the cell or the cell's growth environment. The compositions include an immuno-effective amount of an adjuvant and are described as effective for generating an immune response against Acinetobacter baumannii.
The invention further encompasses antibody and antigen-binding fragments that bind targets of Acinetobacter baumannii, including epitopes defined by a consensus motif (PVDFTVAI from SEQ ID NO:36). Documented antigen recognition, immunogenicity, and functional outcomes are supported using human convalescent IgG ELISA/immunoblot, antigen recognition in multiple strains, and immunization studies in a mouse Acinetobacter pneumonia model, with antigen processing/target-selection approaches including shedome analysis and comparative proteomics.
The defined immunogenic polypeptides and combinations of specified SEQ ID NOs are used in vaccine compositions and immunoassay applications, and antibody compositions are described as therapeutic, prophylactic, and diagnostic compositions. Conservation and prevalence across clinical isolates are stated as part of the selection of antigenic polypeptides expressed during infection.
Claims Coverage
The partial claim set contains two independent claims that define immunogenic compositions. Across the independent claims, the inventive features revolve around (i) a recombinant nucleic-acid encoded immunogenic polypeptide produced in a transformed host cell and formulated with an immuno-effective amount of an adjuvant, and (ii) a specific recombinant antigenic polypeptide (SEQ ID NO:16) with immunostimulatory activity combined with one or more additional polypeptides selected by specified SEQ ID NOs.
Recombinant SEQ ID NO:15 polypeptide immunogenic composition with adjuvant
An isolated polypeptide encoded by a recombinant nucleic acid sequence comprising a polynucleotide sequence having the nucleic acid sequence of SEQ ID NO:15, with an immuno-effective amount of an adjuvant; the polypeptide is isolated by providing a host cell transformed/transfected with an expression vector comprising said recombinant nucleic acid sequence, growing the cell, and purifying the polypeptide from the cell or the cell's growth environment; and the composition is effective in generating an immune response against Acinetobacter baumannii in a subject in need thereof.
SEQ ID NO:16 antigenic polypeptide with immunostimulatory activity plus selected SEQ ID NO polypeptides
An immunogenic composition comprising an isolated recombinant antigenic polypeptide consisting of the amino acid sequence SEQ ID NO:16 having immunostimulatory activity in combination with an immuno-effective amount of an adjuvant; and one or more polypeptides selected from the group consisting of SEQ ID NOs:2, 4, 6, 8, 10, 12, and 14.
Overall, the claims cover immunogenic vaccine-like compositions built around defined Acinetobacter baumannii antigenic polypeptides (SEQ ID NO:15 or SEQ ID NO:16) formulated with an immuno-effective amount of an adjuvant, with SEQ ID NO:15 produced from a recombinant nucleic acid sequence in a transformed/transfected host cell and SEQ ID NO:16 combined with additional polypeptides selected from a defined SEQ ID NO set.
Stated Advantages
Effective in generating an immune response against Acinetobacter baumannii in a subject in need thereof.
Documented Applications
Vaccine composition use and immunoassay use for Acinetobacter baumannii antigenic polypeptides.
Therapeutic, prophylactic, and diagnostic compositions using antibodies or antigen-binding fragments that recognize Acinetobacter baumannii targets.
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