The invention provides proteins and compositions for the treatment and prevention of disease caused by Bordetella pertussis.

The invention provides methods for treating, ameliorating or protecting (preventing) an individual or a patient having or at risk of having heart disease or heart failure, or decreased cardiac function, comprising: providing a cyclic adenosine monophosphate-incompetent (cAMP-incompetent) adenylyl cyclase type 6 (AC6) protein or polypeptide (also called “an AC6mut”), or an AC6mut-encoding nucleic acid or a gene operatively linked to a transcriptional regulatory sequence.

Methods, compositions and kits are provided for treating a subject exposed to or at risk for exposure to a disease agent, methods, compositions and kits having a pharmaceutical composition including at least one recombinant binding protein or a source of expression of the binding protein, wherein the binding protein neutralizes at least one or a plurality of disease agents that are toxins, for example at least one of a Botulinum toxin or an Anthrax toxin.

The present invention discloses a procedure to produce a monomeric and functional form of Bordetella sp, especially B. pertussis, CyaA toxin that can be stably maintained in this functional monodisperse state, even in the absence of any chaotropic agent.

The present invention relates to a method to detect the interaction between a target ligand and a moiety of interest using an adenylate cyclase enzyme (AC) and calmodulin (CaM) as interacting partners, said method comprising: i) expressing in a suitable host cell: (a) a low number of molecules of a first chimeric polypeptide containing AC, and (b) a low number of molecules of a second chimeric polypeptide containing CaM, wherein said AC in said first chimeric polypeptide and/or said CaM in said second chimeric polypeptide has decreased affinity for its interacting partner, wherein said AC in said first chimeric polypeptide is fused to a moiety of interest and said CaM in said second chimeric polypeptide is fused to a target ligand, or conversely, and wherein, when said moiety of interest and said target ligand interact, said AC is activated, and ii) detecting the activation of said AC. The present inventors herein show that only one AC/CaM complex per cell is sufficient to confer a selectable trait to the host cell. Unexpectedly, even less than one AC/CaM complex per cell can be sufficient to confer a selectable trait to the host cell. This surprising result confers a very high sensitivity, that is helpful for screening high affinity interactions, such as antigen-antibody interactions. Moreover, the low expression of the chimeric proteins that is achieved in the present invention allows to characterize toxic moieties, what was not possible before.

The invention is directed to a method of inhibiting prostate cancer cell proliferation using a substance that inhibits the activity of soluble adenylyl cyclase (sAC) protein. The invention also is directed to methods of diagnosing and prognosticating prostate cancer in a subject by evaluating sAC gene expression or sAC protein production in the subject.

The present invention lies in the field of molecular biology, recombinant peptide and protein expression and relates to methods comprising nucleic acid sequences comprising allocrites of T1SSs or fragments thereof for the efficient production of recombinant Pe OIs and Pr OI. The allocrites or fragments thereof improve the expression of PeOI and Pr OI as IB and function as IB-tags.

The invention relates to the use of a polypeptide derived from the adenylate cyclase of a Bordetella sp. (CyaA-derived polypeptide) by deletion of a segment of at least 93 amino acid residues, in particular a polypeptide derived from CyaA of Bordetella pertussis, as an immunomodifying antigen of the TH1/TH17-oriented immune response in an immunogenic composition. The invention relates to a vaccine candidate comprising such CyaA-derived polypeptide, either in an acellular immunogenic composition for active immunization against a condition causally related to the infection of a host by Bordetella sp. or in a combination composition encompassing said acellular immunogenic composition.

The present invention relates to: a composition for detecting a gastric cancer marker comprising a preparation for measuring the expression level or methylation level of mRNA of ADCY3 or a protein thereof; a kit for diagnosing gastric cancer, containing the composition; a method for diagnosing gastric cancer by treating a biological sample with the preparation to ascertain whether a material for complementarily binding to the preparation exists and comparing the amount thereof with a control group; a composition for treating and preventing gastric cancer, containing a preparation capable of inhibiting ADCY3 polynucleotide or ADCY3 polypeptide; and a method for treating gastric cancer by administering the composition to an individual. According to the present invention, it is possible to diagnose gastric cancer with high diagnostic sensitivity and specificity using ADCY3 as a marker for diagnosing gastric cancer, and thus can greatly contribute to reducing mortality due to gastric cancer.

In alternative embodiments, provided are compositions, including products of manufacture and kits, and methods, for treating a heart failure in a subject in need thereof comprising administering to the subject an isolated or recombinant nucleic acid, an isolated or recombinant or chimeric polypeptide, or an engineered cell, as provided herein, thereby treating the subject. In alternative embodiments, the administration reduces left ventricular (LV) hypertrophy, increases LV peak pressure development, reduced cAMP production and/or improves LV peak pressure decay in a pressure-overload in the subject. In alternative embodiments, provided are compositions and methods for: treating, ameliorating, or slowing the progress of, or protecting (preventing) an individual or a patient against heart failure; or, reducing LV hypertrophy, increasing LV peak pressure development, and/or improving LV peak pressure decay in a pressure-overload in an individual in need thereof.