Antigen specific multi epitope-based anti-infective vaccines

Abstract

The invention provides peptide vaccines comprising the signal peptide domain of selected target antigens of intracellular pathogens. The peptide vaccines of the invention contain multiple class II and class I—restricted epitopes and are recognized and presented by the majority of the vaccinated human population. The invention provides in particular anti tuberculosis vaccines. The invention further provides compositions comprising the vaccines as well as their use to treat or prevent infection.

1 . A peptide vaccine comprising at least one signal peptide domain of at least one target protein of an intracellular pathogen. 
     
     
         2 . A peptide vaccine according to  claim 1  , wherein said protein is selected from the group consisting of the Tuberculosis antigens-BPBP1, Antigen 85B, Antigen 85B-Precursor, Lipoprotein 1pqH, Putative lipoprotein IprB precursor, Putative lipoprotein IpqV precursor, Beta gluconase putative, Hypothetical protein MTO 213, Protease, ATP dependent helicase putative, Hypothetical protein MT 1221, BCG, Hypothetical protein Rv0476/MT04941 precursor Hypothetical protein Rv1334/MT1376 precursor, beta-Lactomase precursor; the Malaria P. Falciparum antigens-Circumsporozoit protein precursor, Malaria exported protein-1, Liver stage antigen (LSA-I), Sporozoit surface antigen 2, MSP1, Protein Antigen; the Malaria P. Vivax antigens-Cytoadherence linked asexual protein, Membrane protein PF 12, Exported protein 2, Circumsporozoite-protein related antigen, Circumsporozoite protein precursor, Merozoite surface protein 3 alfa, CTRP adhesive protein invasive stage; The Toxoplasma gondii antigens-GRA-I, SAG1, Surface antigen SAG1, Surface Antigen P22, Rhoptry protein 10; The EBV antigens-Glycoprotein GP85 and BCRF-I, the CMV antigens, Glycoprotein B, RAE-I (human), Unique short US8 glycoprotein precursor, US9 Protein, US7; the human Prion protein; the HIV antigens-Envelope Glycoprotein, reticulocalbin-2 precursor (human), neuronalacetycholine reccep. alfa 3 (human), Envelope polyprotein GP “160 precursor and Transforming membrane receptor-like protein; the Herpes virus 8 antigen-HHV-8 glycoprotein E8-1.8, the Influenza antigens-HA and Neuraminidase and the human HCV related protein CEP and 1 receptor precursor. 
     
     
         3 . A peptide vaccine according to  claim 1 , wherein said signal peptide domain comprises a sequence selected from the group listed in Table 1 (SEQ ID NOs: 1-54). 
     
     
         4 . A peptide vaccine according to  claim 1 , wherein said target protein is a tuberculosis antigen. 
     
     
         5 . A peptide vaccine according to  claim 1 , wherein said peptide vaccine comprises up to about 40 amino acids. 
     
     
         6 . A peptide vaccine according to  claim 1 , wherein said peptide vaccine comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 4, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 12, SEQ ID NO. 13, and SEQ ID NO. 15. 
     
     
         7 . A polypeptide vaccine comprising a recombinant polypeptide comprising at least one signal peptide domain of a target protein of an intracellular pathogen. 
     
     
         8 . A polypeptide vaccine according to  claim 7  wherein said at least one signal peptide domain is selected from the group consisting of SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 4, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 12, SEQ ID NO. 13, and SEQ ID NO. 15. 
     
     
         9 . A polypeptide vaccine according to  claim 8  wherein said vaccine comprises the amino acid sequence of SEQ ID NO. 2, SEQ ID NO. 4, SEQ ID NO. 9, SEQ ID NO. 12, and SEQ ID NO. 13. 
     
     
         10 . A polypeptide vaccine according to  claim 7 , wherein said vaccine further comprises restriction enzyme sites. 
     
     
         11 . A polypeptide vaccine according to  claim 9 , wherein said vaccine comprises the amino acid sequence of SEQ ID NO: 55 or an amino acid sequence having at least 85% homology with SEQ ID NO: 55. 
     
     
         12 . An isolated nucleic acid molecule comprising a nucleotide sequence encoding a peptide according to  claim 1 . 
     
     
         13 . A nucleic acid molecule according to  claim 12 , wherein said nucleic acid molecule is contained in an expression vector. 
     
     
         14 . A nucleic acid vaccine comprising a nucleic acid molecule according to  claim 12 . 
     
     
         15 . An isolated antigen-presenting cell preloaded with the peptide according to  claim 1 . 
     
     
         16 . A pharmaceutical composition comprising at least one peptide vaccine according to any of  claim 1 , and a pharmaceutically acceptable carrier or diluent. 
     
     
         17 . A pharmaceutical composition comprising the antigen-presenting cell according to  claim 15  and a pharmaceutically acceptable carrier or diluent. 
     
     
         18 . A pharmaceutical composition according to  claim 16  adapted for coadministration with other anti-infective agents. 
     
     
         19 . A method of treating or preventing a pathogenic infection comprising administering the pharmaceutical compositions according to  claim 16  to a subject in need thereof.