Incapacitated whole-cell immunogenic bacterial compositions
The invention features incapacitated whole cell bacterial immunogenic compositions produced by infecting a bacterium with Lys minus bacteriophage, which are deficient in the lysin protein. Lys minus bacteriophage retain activity in infection of its appropriate bacterial host, destruction of the bacterial genome, and replication, which are sufficient to inhibit bacterial growth and replication. The resulting, Lys minus-infected bacterium is provided in a state of bacteriostasis, and is not capable of replicating further (e.g., is “incapacitated”). The incapacitated bacterium can then be used as to elicit an immune response for prophylactic and/or therapeutic purposes. The invention thus also features incapacitated bacteria formulated appropriately for use in immunogenic compositions for eliciting an immune response, e.g., for production of antibodies in a non-human host or in a whole cell bacterial vaccine.
1. A method of eliciting an immune response to a bacteria pathogen, the method comprising:
administering a composition to a subject susceptible to infection by a disease caused by a pathogenic bacterium, wherein the composition comprises a whole cell pathogenic bacterium, which bacterium is in a state of irreversible bacteriostasis due to infection with a Lys minus bacteriophage, said administering being in an amount effective to elicit an immune response to the pathogenic bacterium in the host.
2. The method of claim 1 , wherein the pathogenic bacterium is of a genus selected from the group consisting of Mycobacteria, Staphylococci, Vibrio, Enterobacter, Enterococcus, Escherichia, Haemophilus, Neisseria, Pseudomonas, Shigella, Serratia, Salmonella, Streptococcus, Klebsiella and Yersinia.
3. A method of vaccinating a subject against disease caused by a bacterial pathogen, the method comprising:
administering to a subject susceptible disease caused by a pathogenic bacterium a composition comprising a whole cell pathogenic bacterium, which bacterium is in a state of irreversible bacteriostasis due to infection with a Lys minus bacteriophage, said administering being in an amount effective to elicit an immune response to the pathogenic bacterium in the subject.
4. The method of claim 3 , wherein the pathogenic bacterium incapacitated by infection with a Lys minus bacteriophage is genetically engineered to overexpress an endogenous antigen.
5. The method of claim 3 , wherein the pathogenic bacterium is of a genus selected from the group consisting of Mycobacteria, Staphylococci, Vibrio, Enterobacter, Enterococcus, Escherichia, Haemophilus, Neisseria, Pseudomonas, Shigella, Serratia, Salmonella, Streptococcus, Klebsiella and Yersinia.
6. A composition consisting essentially of a bacterium and a pharmaceutically acceptible excipient, wherein the bacterium is in a state of irreversible bacteriostasis due to infection with a Lys minus bacteriophage.
7. The composition of claim 6 , wherein the bacterium is of a genus selected from the group consisting of Mycobacteria, Staphylococci, Vibrio, Enterobacter, Enterococcus, Escherichia, Haemophilus, Neisseria, Pseudomonas, Shigella, Serratia, Salmonella, Streptococcus, Klebsiella and Yersinia.
8. The method of claim 1 , wherein the bacteriophage has a mutation or a deletion in a lysin gene which renders the bacteriophage incapable of producing a functional lysin protein.
9. The method of claim 3 , wherein the bacteriophage has a mutation or a deletion in a lysin gene which renders the bacteriophage incapable of producing a functional lysin protein.
10. The composition of claim 6 , wherein the Lys minus bacteriophage does not produce a functional lysin protein due to the presence of a mutation in the lysin gene.
11. The composition of claim 6 , wherein the Lys minus bacteriophage does not produce a functional lysin protein due to deletion of all or a portion of the lysin gene.
12. The composition of claim 6 , wherein the composition is sterile.
13. A composition comprising a bacterium and a pharmaceutically acceptable excipient, wherein the bacterium is in a state of irreversible bacteriostasis due to infection with a Lys minus bacteriophage.
14. The composition of claim 13 , wherein the bacterium is of a genus selected from the group consisting of Mycobacteria, Staphylococci, Vibrio, Enterobacter, Enterococcus, Escherichia, Haemophilus, Neisseria, Pseudomonas, Shigella, Serratia, Salmonella, Streptococcus, Klebsiella and Yersinia.
15. The composition of claim 13 , wherein the Lys minus bacteriophage does not produce a functional lysin protein due to the presence of a mutation in the lysin gene.
16. The composition of claim 13 , wherein the Lys minus bacteriophage does not produce a functional lysin protein due to deletion of all or a portion of the lysin gene.
17. The composition of claim 13 , wherein the composition is sterile.