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CyaA vector

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BT PHARMA’s CyaA vector system is based on a protein, the Adenylate Cyclase from the bacteria Bordetella pertussis, which infects the respiratory tract of young infants. CyaA is versatile recombinant protein vehicle that can be engineered to present antigens to dendritic cells in such a way that these dendritic cells are:

    • Activated (adjuvant effect),
    • Can process the antigen epitopes via the desired pathway which ultimately results in a strong and specific immune response.

Both Cytotoxic T Lymphocyte (CTL) response (CD8+) and helper T cell (CD4+) can be induced against the T cell epitopes inserted into the CyaA vector system.

Advantages of the CyaA vector

Advantages of the CyaA vector

Advantages of the CyaA vector
    • Versatile vector
    • Large polypeptide delivery 
    • Produces specific and strong immune response- induction of both CTL and helper T cell responses
    • Delivery of multiple antigens/peptides simultaneously 
    • Multiple use – no interfering vector immunity
    • Immunology thoroughly understood
    • Prophylactic and therapeutic use
    • Positive pre-clinical results
    • Low production cost 
    • Strong IP position

The CyaA vector can be used in a broad range of therapeutic indications including: 

    • Viral disease - HPV-induced cancers, HBV, HCV and HIV 
    • Bacterial disease - Tuberculosis
    • Cancers - Melanoma
Recombinant adenylate cyclase (CyaA)
Recombinant adenylate cyclase (CyaA) Shema

  • The adenylate cyclase (CyaA) adhesin of Bordetella pertussis is a bifunctional protein of 1706 residues that is made of a N-terminal catalytic domain of 400 amino acids and a C-terminal part of 1306 residues which is responsible for the binding of the toxin to target cell membrane and the subsequent delivery of the catalytic moiety into the cell cytosol (Sakamoto et al., 1992; Ladant et al., 1999).

 

 

 

In Vivo induction of CTL response by recombinant CyaA

In Vivo induction of CTL response by recombinant CyaA

In Vivo induction of CTL response by recombinant CyaA
In vivo induction of CTL response by recombinant CyaA
  • After CyaA binds to its target cells, via specific recognition of CD11b/CD18 molecules (= αm β2 integrins) that are typical for dendritic cells and macrophages, a conformational change occurs and the catalytic domain is transferred across the cell membrane into the cytosol. The inserted amino-terminal moiety of CyaA is subsequently processed by the proteasome. The released peptides associate with TAP transporter for classic endoplasmic reticulum traffic and presentation in association with MHC I complex on the surface of the cell. Finally, interaction with proper CD8+ T cell induces clonal expansion of antigen-specific cytotoxic T cell Lymphocytes (CTL).
In vivo induction of helper T cell responses of IFN-gamma

In vivo induction of helper T cell responses of IFN-gamma

In vivo induction of helper T cell responses of IFN-gamma
In vivo induction th1 CD4+ responses by recombinant CyaA
  • Once attached to the targeted antigen-presenting cell, some CyaA molecules are also taken up by endocytosis, which translocates the CyaA molecules into lysosomes. In the lysosomal compartment, the protein is degraded and CyaA-derived peptides are exported to the cell surface in association with MHC II class molecules where the complex is presented to CD4+ T cells. This interaction leads to the secreting of TH1 type cytokines, in particular INF-gamma by the CD4+ cells. These lymphocytes help reinforce the strong CD8+ CTL response and contribute to establish T cell memory, which can be of great importance to control infection, recurrence or metastasis of cancer.
PLATFORM CHARACTERISTICS PRODUCTS STAGE
Adenylate Cyclase
  • Specific & strong CTL responses.
  • Class I + Class II MHC presentation.
  • Large polypeptide delivery (>400 aa)
  • Multiple peptides simultaneously.
  • Works without addition of adjuvants.
  • Re-usable: No interfering vector immunity.
  • Low production cost.
  • Immunology thoroughly understood.
  • Confirmed in animal model systems & ex vivo with human cells.
  • Prophylaxis and therapeutic use.
  • Good safety profile.
  • Strong intellectual property position.
ProCervix®
(therapeutic vaccine against HPV induced neoplasia and cancer )
Therapeutic vaccine against cancers of digestive tract
 
Therapeutic vaccine against certain cancers in companion animals
Late pre-clinical
 
Proof of Principle
 
 
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