Targets of Acinetobacter baumannii
Inventors
Urwyler, Simon • Haake, Markus • Rudolf, Michael
Assignees
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Publication Number
US-10603372-B2
Publication Date
2020-03-31
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 antigenic polypeptides and nucleic acids that target Acinetobacter baumannii antigens. It discloses antigenic polypeptide targets expressed during A. baumannii infection, including polypeptide sequence targets defined by SEQ ID NOs 2/4/6/8/10/12/14/16 and corresponding nucleic acids. The described antigens are presented as immunogenic components for generating immune responses against Acinetobacter baumannii in a subject in need thereof.
The invention further discloses immunogenic composition formulations containing the recombinant polypeptides and/or polynucleotides together with an immuno-effective amount of an adjuvant. Exemplified adjuvant and delivery vehicle concepts include virosomes as immunogenic delivery vehicles, along with multiple named adjuvant materials and delivery-related components. The compositions are configured to include immunostimulatory activity for immune response generation against Acinetobacter baumannii.
Antibody-related aspects include antibodies and antigen-binding fragments specific to the targets, including polyclonal/monoclonal antibodies and monoclonal reactivity supported by epitope mapping. The document describes consensus epitope identification for monoclonal reactivity, including a motif PVDFTVAI (SEQ ID NO: 36). It also describes evidence of immunogenicity and functional relevance in binding assays and cell-based assays, and protective activity in a mouse pneumonia model using active and passive immunization.
Claims Coverage
The independent claims (four total: clm-00001, clm-00002, clm-00003, clm-00006) are directed to immunogenic compositions using specific antigen sequences (SEQ ID NO: 9 and/or SEQ ID NO: 10, and optionally a His tag) combined with an immuno-effective amount of an adjuvant, with optional specification of an immunogenic delivery vehicle and/or immunostimulatory activity.
Immunogenic composition with SEQ ID NO: 9 and adjuvant for immune response against Acinetobacter baumannii
An immunogenic composition comprising a polypeptide encoded by a recombinant nucleic acid molecule consisting of the polynucleotide sequence of SEQ ID NO: 9, and an immuno-effective amount of an adjuvant, wherein the composition is effective in generating an immune response against Acinetobacter baumannii in a subject in need thereof.
Isolated recombinant antigenic polypeptide SEQ ID NO: 10 with immunostimulatory activity and adjuvant
An immunogenic composition comprising an isolated recombinant antigenic polypeptide consisting of the amino acid sequence SEQ ID NO: 10 having immunostimulatory activity in combination with an immuno-effective amount of an adjuvant.
Isolated recombinant polypeptide defined by SEQ ID NO: 9 or SEQ ID NO: 10 with a His tag
An isolated recombinant polypeptide consisting of a polypeptide which is encoded by a polynucleotide sequence consisting of the nucleic acid sequence of SEQ ID NO: 9 and a nucleic acid sequence encoding a His tag; or an amino acid sequence consisting of the sequence of SEQ ID NO: 10 and a His tag.
Immunogenic composition with SEQ ID NO: 10 plus His tag and adjuvant
An immunogenic composition comprising an isolated recombinant antigenic polypeptide consisting of the amino acid sequence SEQ ID NO: 10 plus a His tag having immunostimulatory activity in combination with an immuno-effective amount of an adjuvant.
Overall, the claim coverage centers on immunogenic compositions and isolated recombinant antigenic polypeptides defined by SEQ ID NO: 9 and/or SEQ ID NO: 10, with optional His tag inclusion, formulated with an immuno-effective amount of an adjuvant.
Stated Advantages
Generates an immune response against Acinetobacter baumannii in a subject in need thereof.
Provides immunostimulatory activity when formulated with an immuno-effective amount of an adjuvant.
Includes immunogenic delivery vehicles as an effectively immunogenic delivery vehicle component.
Documented Applications
Vaccine compositions for generating an immune response against Acinetobacter baumannii in a subject in need thereof.
Antibody and antigen-binding fragment use for effector functions, neutralization, and diagnostic uses.
Therapeutic/protective evaluation using active and passive immunization protecting in an A. baumannii pneumonia mouse model.
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