1. A bulk ink supply system comprising:
a connector attachable to and detachable from an ink container and including an ink guiding path formed in the connector;
an ink flow path connecting the ink guiding path and an inkjet head of the inkjet printer to supply an ink from the ink guiding path to the inkjet head; and
an on-off valve to allow communication between the ink guiding path and the ink flow path when the ink container is attached to the connector and to hinder communication between the ink guiding path and the ink flow path when the ink container is detached from the connector,
wherein the on-off valve includes
an elastic membrane member, and
a pressing member to deform the elastic membrane member to allow or hinder communication between the ink guiding path and the ink flow path,
wherein the pressing member includes
an ink-container attachment detector capable of contacting with the ink container and movable in a direction where the ink container is attached to or detached from the connector,
a pressing device pressing the ink-container attachment detector in a direction where the ink container is detached from the connector, and
a protruding member fixed to the ink-container attachment detector,
wherein, when the ink container is detached from the connector, the protruding member presses the elastic membrane member using a force applied by the pressing device to hinder communication between the ink guiding path and the ink flow path, and
wherein, when the ink container is attached to the connector, the ink-container attachment detector contacts with the ink container and moves in a direction where the ink container is attached to the connector against the force applied by the pressing device, and the protruding member is provided with respect to the elastic membrane member to allow communication between the ink guiding path and the ink flow path.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. a recombinant attenuated microbial pathogen, which comprises at a least one heterologous nucleic acid molecule encoding a Helicobacter antigen, wherein said pathogen is capable to express said nucleic acid molecule or capable to cause the expression of said nucleic acid molecule in a target cell.
2. The pathogen according to claim 1, which is an enterobacterial cell, especially a Salmonella cell.
3. The pathogen according to claim 1 or 2, which is a Salmonella aro mutant cell.
4. The pathogen according to any of claims 1-3,
wherein the Helicobacter antigen is urease, a urease subunit, an immunologically reactive fragment thereof, or a peptide mimotope thereof.
5. The pathogen according to any one of claims 1-3,
wherein the Helicobacter antigen is a secretory polypeptide from Helicobacter, an immunologically reactive fragment thereof, or a peptide mimotope thereof.
6. The pathogen according to any one of claims 1-3 and 5, wherein the Helicobacter antigen is selected from the group consisting of the antigens AlpA, AlpB, immunologically reactive fragments thereof, or a peptide mimotope thereof.
7. The pathogen according to any one of claims 1-6,
wherein said nucleic acid molecule encoding a Helicobacter antigen is capable to be expressed phase variably.
8. The pathogen according to claim 7,
wherein said nucleic acid molecule encoding the Helicobacter antigen is under control of an expression signal which is substantially inactive in the pathogen and which is capable to be activated by a nucleic acid reorganization caused by a nucleic acid reorganization mechanism in the pathogen.
9. The pathogen according to claim 8,
wherein the expression signal is a bacteriophage promoter, and the activation is caused by a DNA reorganization resulting in the production of a corresponding bacteriophage RNA polymerase in the pathogen.
10. The pathogen according to any one of claims 1-9, further comprising at least one second nucleic acid molecule encoding an immunomodulatory polypeptide, wherein said pathogen is capable to express said second nucleic acid molecule.
11. Pharmaceutical composition comprising as an active agent a recombinant attenuated pathogen according to any one of claims 1-10, optionally together with pharmaceutically acceptable diluents, carriers and adjuvants.
12. Composition according to claim 11, which is a living vaccine, which is suitable for administration to a mucosal surface or via the parenteral route.
13. A method for the preparation of a living vaccine comprising formulating an attenuated pathogen according to any one of claims 1-10 in a pharmaceutically effective amount with pharmaceutically acceptable diluents, carriers andor adjuvants.
14. A method for preparing a recombinant attenuated pathogen according to any one of claims 1-10, comprising the steps:
a) inserting a nucleic acid molecule encoding a Helicobacter antigen into an attenuated pathogen, wherein a recombinant attenuated pathogen is obtained, which is capable of expressing said nucleic acid molecule or is capable to cause expression of said nucleic acid molecule in a target cell, and
b) cultivating said recombinant attenuated pathogen under suitable conditions.
15. The method according to claim 14, wherein said nucleic acid molecule encoding a Helicobacter antigen is located on an extrachromosomal plasmid or inserted in the chromosome.
16. A method for identifying Helicobacter antigens, which raise a protective immune response in a mammalian host, comprising the steps of:
a) providing an expression gene bank of Helicobacter in an attenuated pathogen and
b) screening the clones of the gene bank for their ability to confer protective immunity against a Helicobacter infection in a mammalian host.