Peptides presenting an epitope of a domain of factor H binding protein and methods of use

1. An isolated JAR 4 epitope-containing peptide of at least 9 amino acids in length and comprising the sequence:

DX 1 X 2

wherein

X 1 is histidine (H) or aspartic acid (D);

X 2 is lysine (K) or arginine (R);

the aspartic acid residue (D) of the DX 1 X 2 sequence does not contain an N-terminal amino group;

the peptide contains at least 3 amino acid residues positioned immediately C-terminal to the X 2 , wherein the at least 3 amino acid residues are selected from:

LEGTE,

(SEQ ID NO: 1)

TGCA,

(SEQ ID NO: 2)

TQL,

AQT,

SGC,

TANQ,

(SEQ ID NO: 3)

IWP,

HML,

and

HGF,

with the proviso that when the at least 3 amino acid residues are TANQ (SEQ ID NO:3), the peptide comprises a histidine (H) immediately N-terminal to the aspartic acid residue (D) of the DX 1 X 2 sequence, and when the at least 3 amino acid residues are TGCA (SEQ ID NO:2), the peptide comprises a tyrosine (Y) immediately N-terminal to the aspartic acid residue (D) of the DX 1 X 2 sequence;

the peptide does not comprise a full-length A domain of a factor H binding protein; and

the peptide is specifically bound by JAR 4 monoclonal antibody secreted by the hybridoma deposited as ATCC Accession No. PTA-8943.

2. The isolated JAR 4 epitope-containing peptide of claim 1 , wherein the X 1 is histidine (H) and the X 2 is lysine (K).

3. The isolated JAR 4 epitope-containing peptide of claim 2 , wherein the at least 3 amino acid residues are LEGTE (SEQ ID NO:1), TQL, AQT, TANQ (SEQ ID NO:3), or HGF.

4. The isolated JAR 4 epitope-containing peptide of claim 1 , wherein the X 1 is aspartic acid (D) and the X 2 is lysine (K).

5. The isolated JAR 4 epitope-containing peptide of claim 4 , wherein the at least 3 amino acid residues are TGCA (SEQ ID NO: 2).

6. The isolated JAR 4 epitope-containing peptide of claim 1 , wherein the X 1 is histidine (H) and the X 2 is arginine (R).

7. The isolated JAR 4 epitope-containing peptide of claim 6 , wherein the at least 3 amino acid residues are SGC, IWP, or HML.

8. An isolated peptide of at least 9 amino acids in length, and comprising at least 7 contiguous amino acid residues of an amino acid sequence of:

        H D H K L E G T E,

(SEQ ID NO: 14)

C G G V Y D D K T G C A,

(SEQ ID NO: 15)

        H D H K T Q L D P,

(SEQ ID NO: 16)

W T L A V F D H K A Q T,

(SEQ ID NO: 17)

  G C M G Y D H R S G C V,

(SEQ ID NO: 18)

        F H D H K T A N Q,

(SEQ ID NO: 19)

          H D H R I W P L D V T A,

(SEQ ID NO: 21)

          K D H R H M L W P E E S,

(SEQ ID NO: 25)

or

          H D H  K  H G F Q E P A S,

(SEQ ID NO: 29)

wherein

the peptide contains the DHK, DDK, or DHR sequence,

the DHK, DDK, or DHR sequence does not contain an N-terminal amino group when present at the peptide N-terminus; and

the peptide is specifically bound by JAR 4 monoclonal antibody secreted by the hybridoma deposited as ATCC Accession No. PTA-8943.

9. An isolated peptide of at least 9 amino acids in length and comprising the contiguous amino acid sequence of:

(SEQ ID NO: 22)

N D E R Q M S D W Y R A,

or

(SEQ ID NO: 23)

H V H R G S Q G G Q R Q.

10. An isolated peptide of at least 9 amino acids in length and comprising the contiguous amino acid sequence of:

(SEQ ID NO: 20)

W R W C G F E R C P E G,

(SEQ ID NO: 30)

S D W G W G G R A E Q H,

(SEQ ID NO: 31)

V G W C G F E R C S S A,

(SEQ ID NO: 24)

L E W C G F S R C E V G,

(SEQ ID NO: 26)

      L C Q E R L S Q R C G V,

(SEQ ID NO: 27)

W V L C G Q G C G G T A,

or

(SEQ ID NO: 28)

R C Q V Q V M V L C A L.

11. The isolated peptide of claim 1 wherein said peptide is conjugated to a fatty acid residue at the N-terminus.

12. An isolated nucleic acid encoding the peptide according to claim 1 .

13. An immunogenic composition comprising:

the peptide according to claim 1 ; and

a pharmaceutically acceptable excipient.

14. The immunogenic composition of claim 13 , wherein the peptide is coupled to a carrier molecule.

15. The immunogenic composition of claim 13 , wherein the composition comprises an adjuvant.

16. The immunogenic composition of claim 13 , further comprising a polypeptide comprising an amino acid sequence of a factor H binding protein (fHbp) that is specifically bound by at least one of the monoclonal antibodies JAR 3, JAR 5, JAR 11, and JAR 13.

17. The immunogenic composition of claim 13 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus.

18. The immunogenic composition of claim 17 , wherein said fatty acid residue comprises a lauroyl group.

19. The immunogenic composition of claim 13 , wherein said composition comprises outer membrane vesicles, membrane vesicles, or a mixture of outer membrane vesicles and membrane vesicles obtained from Neisseria meningitidis.

20. The immunogenic composition of claim 13 , wherein said composition comprises an fHbp.

21. The immunogenic composition of claim 13 , wherein said composition comprises the r3C vaccine.

22. A method of inducing an immune response to Neisseria meningitidis in a subject comprising:

administering the immunogenic composition according to claim 13 to the subject in an amount effective to elicit production of antibodies to the peptide in the subject.

23. A method of inducing an immune response to Neisseria meningitidis in a subject, comprising:

administering to the subject an immunogenic composition comprising a JAR 4 epitope-containing peptide of at least 9 amino acids in length and comprising the sequence:

DX 1 X 2

wherein

X 1 is histidine (H) or aspartic acid (D);

X 2 is lysine (K) or arginine (R);

the aspartic acid residue (D) of the DX 1 X 2 sequence does not contain an N-terminal amino group;

the peptide does not comprise a full-length A domain of a factor H binding protein;

the peptide is specifically bound by JAR 4 monoclonal antibody secreted by the hybridoma deposited as ATCC Accession No. PTA-8943; and

wherein said administering is effective to elicit production of antibodies to the peptide in the subject.

24. The method of claim 23 , wherein the X 1 is histidine (H) and the X 2 is lysine (K).

25. The method of claim 24 , wherein the peptide comprises the amino acid sequence of LEGTE (SEQ ID NO:1), TQL, AQT, TANQ (SEQ ID NO:3), or HGF immediately C-terminal to the X 2 .

26. The method of claim 23 , wherein the X 1 is aspartic acid (D) and the X 2 is lysine (K).

27. The method of claim 24 , wherein the peptide comprises the amino acid sequence of TGCA (SEQ ID NO: 2) immediately C-terminal to the X 2 .

28. The method of claim 23 , wherein the X 1 is histidine (H) and the X 2 is arginine (R).

29. The method of claim 28 , wherein the peptide comprises the amino acid sequence of SGC, IWP, or HML immediately C-terminal to the X 2 .

30. The method of claim 28 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus.

31. A method of making an immunogenic composition against Neisseria meningitidis comprising combining the isolated peptide of claim 1 , with a factor H binding protein.

32. The method of claim 31 , wherein said factor H binding protein is expressed by a Neisseria meningitidis cell that is genetically modified to express the factor H binding protein.

33. The method of claim 32 , wherein said Neisseria meningitidis cell is genetically modified to attenuate the expression of lpxL1 gene.

34. The method of claim 33 , comprising combining said isolated peptide with vesicles obtained from a Neisseria meningitidis cell that is genetically modified to express factor H binding protein.

35. The method of claim 34 , wherein said vesicles are treated with a detergent.

36. The method of claim 31 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus.

37. The immunogenic composition of claim 11 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus through a linker.

38. The immunogenic composition of claim 17 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus through a linker.

39. The method of claim 30 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus through a linker.

40. The method of claim 36 , wherein said peptide is conjugated to a fatty acid residue at the N-terminus through a linker.