Prevention, treatment and diagnosis of
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. A method of reducing the secerity of a P. gingivalis -related disease or condition in a subject, comprising administering to the subject an antibody raised against a chimeric or fusion 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 the amino acid sequence that is the same as, or at least 90% homologous to, the sequence shown in any one of SEQ ID NOs: 1-34; and
(B) said second peptide or polypeptide is selected from the group consisting of:
(i) the amino acid sequence that is the same as, or at least 90% homologous to, the sequence of an adhesin domain of the Lys-X-proteinase of P. gingivalis shown in any one of SEQ ID NOs: 35-37 and 40-43; and
(ii) the amino acid sequence that is the same as, or at least 90% homologous to, the sequence of an adhesin domain of the Arg-X-proteinase of P. gingivalis shown in any one of SEQ ID NOs: 38-39 and 44-46;
(iii) the amino acid sequence that is the same as, or at least 90% homologous to, the sequence of a HagA adhesin domain of P. gingivalis shown in any one of SEQ ID NOs: 80-82; and
(iv) the amino acid sequence that is the same as or at least 90% homologous to, the sequence shown in any one of SEQ ID NOs: 69-79 and 83 to 85.
2. The method according to claim 1 , wherein the first peptide of the chimeric or fusion peptide comprises or consists of a sequence shown in one of more of SEQ ID NOs. 3 to 26.
3. The method according to claim 1 , wherein the antibody is a monoclonal antibody.
4. The method according to claim 1 , wherein:
(A) the first peptide of the chimeric or fusion protein comprises a sequence 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), RAS1 (SEQ ID NO: 31), RAS2 (SEQ ID NO:32), KAS3 (SEQ ID NO: 33), and PAS1R (SEQ ID NO: 34), and
(B) the second peptide or polypeptide of the chimeric or fusion protein comprises a sequence (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.
5. The method according to claim 1 , wherein the chimeric or fusion protein comprises at least two sequences that are the same as, or at least 90% homologous to, a sequence 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), RAS1 (SEQ ID NO: 31), RAS2 (SEQ ID NO: 32), RAS3 (SEQ ID NO: 33), and PAS1R (SEQ ID NO: 34).
6. The method according to claim 1 , wherein said first peptide of the chimeric or fusion protein comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 3-34 and sequences at least 90% homologous thereto.
7. The method according to claim 1 , wherein said second peptide or polypeptide of the chimeric or fusion protein comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 35-39 and sequences at least 90% homologous thereto.
8. The method according to claim 1 , wherein:
(a) said first peptide of the chimeric or fusion protein comprises the amino acid sequence that is the same as or at least 90% homologous to the sequence shown in any one of SEQ ID NOs: 27-30 and said second peptide or polypeptide of the chimeric or fusion protein comprises the amino sequence that is the same as or at least 90% homologous to the sequence shown in any one of SEQ ID NOs: 36-37; or
(b) said first peptide of the chimeric or fusion protein comprises the amino acid sequence that is the same as or at least 90% homologous to the sequence shown in any one of SEQ ID NOs: 31-34 and said second peptide or polypeptide of the chimeric or fusion protein comprises a sequence that is the same as or at least 90% homologous to SEQ ID NO:39.
9. The method according to claim 1 , wherein said second peptide or polypeptide of the chimeric or fusion protein comprises or consists of the sequence shown in one or more of SEQ ID NOs. 69 to 79 or one or more of SEQ ID NOs. 83 to 85.
10. The method according to claim 9 , wherein said first peptide of the chimeric or fusion protein comprises or consists of the sequence shown in one of more of SEQ ID NOs. 3 to 26.
11. The method according to claim 1 , wherein said first peptide of the chimeric or fusion protein comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO:28 and said second peptide or polypeptide of the chimeric or fusion protein comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO: 37.
12. The method according to claim 1 , wherein said first peptide of the chimeric or fusion protein comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO:27 and said second peptide or polypeptide comprises the sequence that is the same as or at least 90% homologous to the sequence shown in SEQ ID NO:36.