Compositions and methods comprising KLK3 of FOLH1 antigen
The present invention provides KLK3 peptides, FOLH1 peptides, recombinant polypeptides comprising same, recombinant nucleotide molecules encoding same, recombinant Listeria strains comprising same, and immunogenic and therapeutic methods utilizing same.
1. A recombinant Listeria strain encoding a recombinant fusion peptide consisting of a KLK3 peptide operatively linked to a non-KLK3 peptide, wherein said non-KLK3 peptide is a N-terminal non-hemolytic listeriolysin (LLO) peptide, said fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide) thereto, wherein said N-terminal LLO peptide enhances the immunogenicity of the fusion peptide.
2. A nucleotide molecule encoding a recombinant polypeptide comprising a fusion peptide consisting of a KLK3 peptide operatively linked to a non-KLK3 peptide, wherein said non-KLK3 peptide is an N-terminal non-hemolytic listeriolysin (LLO) peptide, said KLK3 fusion peptide consisting of the sequence of SEQ ID NO: 54 or a sequence at least 99% homologous (throughout the length of the peptide) thereto wherein said N-terminal LLO peptide enhances the immunogenicity of the fusion peptide.
3. A vaccine comprising the nucleotide molecule of claim 2 and an adjuvant.
4. A recombinant vaccine vector comprising the nucleotide molecule of claim 2 .
5. The recombinant Listeria strain of claim 1 , wherein said recombinant Listeria strain is an auxotrophic Listeria.
6. The recombinant Listeria strain of claim 5 , wherein said auxotrophic Listeria strain is a dal/dat mutant.
7. The recombinant Listeria strain of claim 5 , wherein said auxotrophic Listeria further comprises a deletion in the endogenous ActA gene.
8. The recombinant Listeria strain of claim 5 , wherein said auxotrophic Listeria strain comprises an episomal expression vector comprising a metabolic enzyme that complements the auxotrophy of said auxotrophic Listeria strain.
9. The recombinant Listeria strain of claim 8 wherein said metabolic enzyme is an alanine racemase enzyme.
10. The recombinant Listeria strain of claim 8 , wherein said metabolic enzyme is a D-amino acid transferase enzyme.
11. The recombinant Listeria of claim 1 , wherein said recombinant Listeria is a recombinant Listeria monocytogenes strain.
12. The vaccine of claim 3 , wherein said adjuvant comprises Montanide ISA 51, GM-CSF, KLH, a cytokine, a growth factor, a cell population, QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, an interleukin, an unmethylated CpG oligonucleotide, quill glycosides, monophosphoryl lipid A, a liposomes, a bacterial mitogen, a bacterial toxin, or a chemokine, or any combination thereof.
13. An immunogenic composition comprising the recombinant Listeria strain of claim 1 and an adjuvant.
14. The composition of claim 13 , wherein said adjuvant comprises Montanide ISA 51, GM-CSF, KLH, a cytokine, a growth factor, a cell population, QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, an interleukin, an unmethylated CpG oligonucleotide, quill glycosides, monophosphoryl lipid A, a liposomes, a bacterial mitogen, a bacterial toxin, or a chemokine, or any combination thereof.
15. The recombinant Listeria strain of claim 5 , wherein said auxotrophic Listeria strain further comprises a deletion in the endogenous ActA gene and is a dal/dat mutant.