Prevention, treatment and diagnosis of p.gingivalis infection

Abstract

The invention relates to generation and use of cellular and humoral responses for the prevention and treatment of P. gingivalis related conditions and diseases.

1 .- 70 . (canceled) 
     
     
         71 . A chimeric or fusion protein for inducing an immune response to  P. gingivalis , the protein comprising a first peptide joined directly or through a linker to a second peptide or polypeptide, wherein:
 (A) said first peptide comprises a region of a  P. gingivalis  trypsin-like enzyme selected from the group consisting of:
 (i) part of, or all of a sequence that is the same as, or homologous to the sequence shown in SEQ ID No:1; and 
 (ii) part of, or all of a sequence that is the same as, or homologous to the sequence shown in SEQ ID No:2; and 
   (B) said second peptide or polypeptide comprises an adhesin domain of  P. gingivalis , or fragment thereof, selected from the group consisting of:
 (i) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Lys-X-proteinase of  P. gingivalis;    
 (ii) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Arg-X-proteinase of  P. gingivalis ; and 
 (iii) part of, or all of a sequence that is the same as, or homologous to the sequence of a HagA adhesin domain of  P. gingivalis.    
   
     
     
         72 . The chimeric or fusion protein according to  claim 71 , wherein said first peptide comprises a sequence selected from the group consisting of SEQ ID NOs: 3-34 and sequences at least 90% homologous thereto. 
     
     
         73 . The chimeric or fusion protein according to  claim 71 , wherein said second peptide or polypeptide comprises a sequence selected from the group consisting of SEQ ID NOs: 35-39. 
     
     
         74 . The chimeric or fusion protein according to  claim 71 , wherein:
 (a) said first peptide comprises a sequence that is the same as or homologous to a sequence selected from the group consisting of SEQ ID NOs: 27-30 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to a sequence selected from the group consisting of SEQ ID NOs: 36-37; or   (b) said first peptide comprises a sequence that is the same as or homologous to a sequence selected from the group consisting of SEQ ID NOs: 31-34 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to SEQ ID NO:39.   
     
     
         75 . A chimeric or fusion protein according to  claim 71 , wherein:
 the C-terminal residue of said first peptide is covalently linked directly or through a linker that is either (i) up to 15 amino acids in length, or (ii) less than 5 amino acids in length, to either (a) the N-terminal residue or (b) the C-terminal residue of said second peptide or polypeptide, or   the N-terminal residue of said first peptide is covalently linked directly or through a linker that is either (i) up to 15 amino acids in length, or (ii) less than 5 amino acids in length, to either (a) the N-terminal residue or (b) the C-terminal residue of said second peptide or polypeptide.   
     
     
         76 . A composition comprising a chimeric or fusion protein according to  claim 71 . 
     
     
         77 . The composition according to  claim 76 , further comprising an adjuvant. 
     
     
         78 . A method of preventing or reducing the incidence or severity of a  P. gingivalis -related condition or disease in a subject, comprising administering to the subject a chimeric or fusion protein of  claim 71 . 
     
     
         79 . An antibody raised against the chimeric or fusion protein of  claim 71 . 
     
     
         80 . The antibody according to  claim 79 , wherein the antibody is a monoclonal antibody. 
     
     
         81 . A method of preventing or reducing the severity of a  P. gingivalis -related disease or condition in a subject, comprising administering to the subject the antibody of  claim 79 . 
     
     
         82 . A nucleic acid molecule comprising a sequence encoding the chimeric or fusion protein of  claim 71 . 
     
     
         83 . A method for the diagnosis or monitoring of a  P. gingivalis -related condition or disease in a subject, which comprises assaying a biological sample from said subject with the chimeric or fusion protein of  claim 71  to detect anti- P. gingivalis  antibodies. 
     
     
         84 . A method for the diagnosis or monitoring of a  P. gingivalis -related condition or disease in a subject, which comprises assaying a biological sample from said subject with the antibody according to  claim 79 , to detect the presence of  P. gingivalis.    
     
     
         85 . A chimeric or fusion protein according to  claim 71  wherein the second peptide or polypeptide comprises or consists of a sequence shown in one or more of SEQ ID No: 69 to 79 or one or more of SEQ ID No: 83 to 85. 
     
     
         86 . A chimeric or fusion protein according to  claim 90  wherein the first peptide comprises or consists of a sequence shown in one of more of SEQ ID No: 3 to 26 or one or more of SEQ ID No: 64 to 68. 
     
     
         87 . A chimeric or fusion protein for inducing an immune response to  P. gingivalis , comprising:
 (A) a first peptide with a sequence from a  P. gingivalis  trypsin-like enzyme selected from the group consisting of KAS1 (SEQ ID NO: 27), KAS2 (SEQ ID NO: 28), KAS3 (SEQ ID NO: 29), PAS1K (SEQ ID NO: 30), KAS4 (SEQ ID NO: 64), KAS5 (SEQ ID NO: 65), KAS6 (SEQ ID NO: 66), RAS1 (SEQ ID NO: 31), RAS2 (SEQ ID NO: 32), RAS3 (SEQ ID NO: 33), KAS4 (SEQ ID NO: 67), RAS5 (SEQ ID NO: 68), and PAS1R (SEQ ID NO: 34), and   (B) a second peptide or polypeptide comprises an adhesin domain of  P. gingivalis , or fragment thereof, (i) selected from the group consisting of KA1 (SEQ ID NO: 35), KA2 (SEQ ID NO: 40), KA3 (SEQ ID NO: 41), KA4 (SEQ ID NO: 42), KA5 (SEQ ID NO: 43), RA1 (SEQ ID NO: 38), RA2 (SEQ ID NO: 44), RA3 (SEQ ID NO: 45), RA4 (SEQ ID NO: 46), HA1 (SEQ ID NO: 80), HA1* (SEQ ID NO: 81), HA1** (SEQ ID NO: 82), or (ii) selected from the group consisting of SEQ ID NOs.: 69-79, or (iii) selected from the group consisting of SEQ ID NOs.: 83-85.   
     
     
         88 . A chimeric or fusion protein for inducing an immune response to  P. gingivalis , comprising at least two sequences that are the same as, or homologous to a sequence from a  P. gingivalis  trypsin-like enzyme selected from the group consisting of KAS1 (SEQ ID NO: 27), KAS2 (SEQ ID NO: 28), KAS3 (SEQ ID NO: 29), PAS1K (SEQ ID NO: 30), KAS4 (SEQ ID NO: 64), KAS5 (SEQ ID NO: 65), KAS6 (SEQ ID NO: 66), RAS1 (SEQ ID NO: 31), KAS2 (SEQ ID NO: 32), RAS3 (SEQ ID NO: 33), RAS4 (SEQ ID NO: 67), RAS5 (SEQ ID NO: 68), and PAS1R (SEQ ID NO: 34); and at least one sequence that comprises an adhesin domain of  P. gingivalis , or fragment thereof, selected from:
 (i) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Lys-X-proteinase of  P. gingivalis ; and   (ii) part of, or all of a sequence that is the same as, or homologous to the sequence of an adhesin domain of the Arg-X-proteinase of  P. gingivalis ; and   (iii) part of, or all of a sequence that is the same as, or homologous to the sequence of a HagA adhesin domain of  P. gingivalis.      
     
     
         89 . The chimeric or fusion protein according to  claim 74  wherein said first peptide comprises a sequence that is the same as or homologous to the sequence set out in SEQ ID NO:28 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to the sequence shown in SEQ ID No: 37. 
     
     
         90 . The chimeric or fusion protein according to  claim 74  wherein said first peptide comprises a sequence that is the same as or homologous to the sequence set out in SEQ ID NO:27 and said second peptide or polypeptide comprises a sequence that is the same as or homologous to the sequence shown in SEQ ID No: 36.