Targets of Acinetobacter baumannii

Inventors

Urwyler, SimonHaake, MarkusRudolf, Michael

Assignees

Aridis Pharmaceuticals Inc

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Publication Number

US-10098942-B2

Patent

Publication Date

2018-10-16

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 document describes antigenic outer-membrane polypeptides from Acinetobacter baumannii, including AB023, AB024, AB025, AB030, AB031L1, FimA, CsuAB, and OmpA, with corresponding nucleic acids and variants (SEQ ID NOs 1–16). The polypeptides and recombinant nucleic acids are presented as antigenic components for immunogenic composition, including vaccine composition and diagnostic use.

The document addresses the problem of identifying antigenic targets of Acinetobacter baumannii that are broadly clinically relevant and immunogenic. Selection criteria are described using shedome analysis, comparative proteomics, and specific target identification using convalescent patient sera, with conservation and/or prevalence across multiple A. baumannii strains being supported in tables (e.g., Table 2 and Table 5).

The document further describes that encoded polypeptides are immunostimulatory and include antibody and epitope-related information, including an antibody target/epitope consensus motif PVDFTVAI (SEQ ID NO: 36). Human convalescent sera recognition of the antigens is described (ELISA; Fig. 1), and immunogenicity evidence is provided using rabbit immunization and target-specific responses, together with functional binding and additional assays.

Claims Coverage

Three independent claims are directed to immunogenic compositions containing isolated recombinant Acinetobacter baumannii antigenic polypeptides or polypeptides encoded by recombinant nucleic acids, combined with an immuno-effective or effective amount of an adjuvant to generate or induce an immune response against Acinetobacter baumannii. Across the independent claims, the inventive features focus on specific encoded polypeptide sequences and inclusion of an adjuvant at an immuno-effective/effective amount.

Recombinant nucleic acid-encoded polypeptide with SEQ ID NO: 5 and immuno-effective adjuvant

An immunogenic composition comprising an isolated polypeptide encoded by a recombinant nucleic acid molecule comprising a polynucleotide having the nucleic acid sequence of SEQ ID NO: 5, 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: 6 with immunostimulatory activity and immuno-effective adjuvant

An immunogenic composition comprising an isolated recombinant antigenic polypeptide consisting of the amino acid sequence SEQ ID NO: 6 having immunostimulatory activity in combination with an immuno-effective amount of an adjuvant.

Isolated recombinant antigenic polypeptide SEQ ID NO: 6 with effective adjuvant to induce immune response

An immunogenic composition comprising an isolated recombinant antigenic polypeptide comprising the amino acid sequence of SEQ ID NO: 6, and the composition comprising an effective amount of an adjuvant, wherein the composition induces an immune response against Acinetobacter baumannii.

Collectively, the independent claims cover immunogenic compositions built around isolated recombinant Acinetobacter baumannii antigenic polypeptides encoded by specified sequences, paired with an immuno-effective/effective adjuvant amount, to generate or induce an immune response against Acinetobacter baumannii.

Stated Advantages

Effective in generating an immune response against Acinetobacter baumannii in a subject in need thereof.

Immunostimulatory activity when formulated with an immuno-effective amount of an adjuvant.

Induces an immune response against Acinetobacter baumannii.

Documented Applications

Vaccine and diagnostic use based on antigenic outer-membrane polypeptides from Acinetobacter baumannii and their nucleic acids/variants.

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