Genus-wide chlamydial peptide vaccine antigens
View Patent ↗Peptides generated from a random library that are bound by a monoclonal antibody to Chlamydial glycolipid exoantigen (GLXA) and thus mimic this antigen are disclosed. Peptides that correspond to antigen-binding regions of an anti-idiotypic antibody (mAb2) specific for anti-GLXA antibody (Ab1) which act as molecular mimics of GLXA are also disclosed used as immunogens to induce broadly reactive genus-specific anti-chlamydial antibodies. These peptides and immunogenic DNA encoding the mAb2-like peptides, microparticle or nanoparticle formulations and other formulations of these peptides are disclosed as are methods for immunizing subjects to obtain genus-specific anti-chlamydial antibodies and to treat or prevent Chlamydia -associated or induced rheumatoid arthritis.
1. An isolated immunogenic peptide of at least about 10 amino acids and not longer than about 30 amino acids, which peptide mimics immunologically the structure of chlamydia genus-specific glycolipid exoantigen (GLXA) and binds to an anti-GLXA antibody, and/or
when the peptide is administered to a mammalian subject in an adequate amount and in immunogenic form, it induces a protective antibody response that is measurable in:
an immunoassay that measures binding to chlamydia organisms of multiple chlamydial species; and/or
an immunoassay or biological assay that measures inhibition of function growth or survival of said Chlamydia organisms,
wherein the peptide comprises:
(a) Pep1, SEQ ID NO:1;
(b) Pep2, SEQ ID NO:2;
(c) Pep4, SEQ ID NO:4;
(d) Pep5, SEQ ID NO:5;
(e) Pep6, SEQ ID NO:6;
(f) Pep7, SEQ ID NO:7;
(g) Pep8, SEQ ID NO:8;
(h) Pep9, SEQ ID NO:9;
(i) Pep10, SEQ ID NO:10;
(j) Pep14, SEQ ID NO:14.
2. The immunogenic peptide of claim 1 wherein the anti-GLXA antibody to which the peptide binds is a monoclonal antibody (mAb) produced by a hybridoma cell line deposited in the ATCC as accession number HB-11300.
3. An immunogenic peptide that consists of
(a) one of the peptides (a)-(j) of claim 1 ;
(b) Pep 12, SEQ ID 12; or
(c) Pep 13, SEQ ID 13.
4. An immunogenic cyclic peptide comprising
(i) the immunogenic peptide (a)-(1) of claim 1 .
5. The immunogenic cyclic peptide of claim 4 , the linear sequence of which is selected from the group consisting of
SEQ ID NO:15; SEQ ID NO:16; SEQ ID NO:18; SEQ ID NO:19; SEQ ID NO:20; SEQ ID NO:21;
SEQ ID NO:22; SEQ ID NO:23; SEQ ID NO:24; SEQ ID NO:25; SEQ ID NO:29; SEQ ID NO:30;
SEQ ID NO:31; SEQ ID NO:32, SEQ ID NO:34; SEQ ID NO:35; SEQ ID NO:36; SEQ ID NO:37; SEQ ID NO:45; SEQ ID NO:46; SEQ ID NO:48; SEQ ID NO:49; SEQ ID NO:50; SEQ ID NO:51;
SEQ ID NO:38; SEQ ID NO:39; SEQ ID NO:40; SEQ ID NO:44; SEQ ID NO:52; SEQ ID NO:53; SEQ ID NO:54; and SEQ ID NO:58.
6. An immunogenic linear peptide oligomer or multimer that comprises between about two and about 20 repeats of the same or different peptides of claim 1 , or Pep3 (SEQ ID NO:3), Pep11 (SEQ ID NO:11), Pep12 (SEQ ID NO:12) or Pep13 (SEQ ID NO:13),
wherein, when the oligomer or multimer comprises Pep3 (SEQ ID NO:3), Pep11 (SEQ ID NO:11), Pep12 (SEQ ID NO:12) or Pep13 (SEQ ID NO:13), the oligomer or multimer also includes at least one of peptides (a)-(j) from claim 1 .
7. The peptide oligomer or multimer of claim 6 that comprises one or more linkers, each between any two adjacent repeating units of said peptide.
8. The peptide oligomer or multimer of claim 6 that is cyclized.
9. An immunogenic tandem oligomeric peptide that comprises two or three repeats of the peptide of claim 1 linked in tandem.
10. Pep11 (SEQ ID NO:11) or Pep12 (SEQ ID NO:12) or Pep13 (SEQ ID NO:13) is covalently linked to said functional groups.
11. An immunogenic composition comprising:
(a) the immunogenic peptide of claim 1 or Pep3 (SEQ ID NO:3), Pep11 (SEQ ID NO:11), Pep12 (SEQ ID NO:12) or Pep13 (SEQ ID NO:13); and
(b) an immunologically and pharmaceutically acceptable carrier or excipient, wherein, when (a) is Pep11 (SEQ ID NO:11), Pep3 (SEQ ID NO:3), Pep12 (SEQ ID NO:12) or Pep13 (SEQ ID NO:13),
(i) the peptide is linked or conjugated to an immunogenic carrier molecule, or
(ii) the composition further comprises an adjuvant, an immunostimulatory protein different from said peptide or a CpG oligonucleotide.
12. The immunogenic composition of claim 11 that further comprises microspheres, microparticles or nanoparticles comprising a solid matrix formed of a pharmaceutically acceptable polymer which microspheres, microparticles or nanoparticles comprise said peptide.
13. The immunogenic composition of claim 11 wherein the peptide is in the form of a linear oligomer or multimer.
14. The immunogenic composition of claim 11 , wherein the peptide is linked to a filamentous bacteriophage.
15. The immunogenic composition of claim 11 that further comprises an adjuvant, an immunostimulatory protein different from said immunogenic peptide, or a CpG oligonucleotide.
16. A method of immunizing a mammalian subject against Chlamydia infection which comprises administering to said subject an effective immunogenic amount of the peptide of claim 1 or peptide Pep3 (SEQ ID NO:3), Pep11 (SEQ ID NO:11), Pep12 (SEQ ID NO:12) or Pep13 (SEQ ID NO:13) resulting in a chlamydial antigen GLXA-specific antibody response that is Chlamydia genus-specific.
17. A method of immunizing a mammalian subject against Chlamydia infection which comprises administering to said subject an effective immunogenic amount of the peptide of claim 6 , resulting in a chlamydial antigen GLXA-specific antibody response that is Chlamydia genus-specific.
18. A method of immunizing a mammalian subject against Chlamydia infection which comprises administering to said subject an effective immunogenic amount of the composition of claim 11 , resulting in a chlamydial antigen GLXA-specific antibody response that is Chlamydia genus-specific.
19. The method of claim 16 wherein the antibody response is a neutralizing antibody response that prevents or inhibits infectivity, growth, spread of, or pathogenesis by, said Chlamydia in said subject.
20. The method of claim 19 wherein the subject is a human.
21. An immunogenic composition comprising
(a) the immunogenic peptide of claim 5 or peptide Pep3 (SEQ ID NO:3) or Pep11 (SEQ ID NO:11); and
(b) an immunologically and pharmaceutically acceptable carrier or excipient, wherein, when (a) is Pep11 (SEQ ID NO:11) or Pep3 (SEQ ID NO:3),
(i) the peptide is linked or conjugated to an immunogenic carrier molecule, or
(ii) the composition further comprises an adjuvant, an immunostimulatory protein different from said peptide or a CpG oligonucleotide.
22. The immunogenic composition of claim 21 that further comprises microspheres, microparticles or nanoparticles comprising a solid matrix formed of a pharmaceutically acceptable polymer which microspheres, microparticles or nanoparticles comprise said peptide.
23. A method of immunizing a mammalian subject against Chlamydia infection which comprises administering to said subject an effective immunogenic amount of the peptide of claim 3 resulting in a chlamydial antigen GLXA-specific antibody response that is Chlamydia genus-specific.
24. A method of immunizing a mammalian subject against Chlamydia infection which comprises administering to said subject an effective immunogenic amount of the composition of claim 21 , resulting in a chlamydial antigen GLXA-specific antibody response that is Chlamydia genus-specific.
25. The method of claim 24 wherein the antibody response is a neutralizing antibody response that prevents or inhibits infectivity, growth, spread of, or pathogenesis by, said Chlamydia in said subject.
26. The method of claim 25 wherein the subject is a human.