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. 1996 Nov;89(3):331–337. doi: 10.1046/j.1365-2567.1996.d01-754.x

Opsonic human antibodies from an endemic population specific for a conserved epitope on the M protein of group A streptococci.

E R Brandt 1, W A Hayman 1, B Currie 1, J Carapetis 1, Y Wood 1, D C Jackson 1, J Cooper 1, W D Melrose 1, A J Saul 1, M F Good 1
PMCID: PMC1456558  PMID: 8958044

Abstract

This study demonstrates the presence of epitope-specific opsonic human antibodies in a population living in an area endemic for group A streptococci (GAS) infection. Antibodies recognizing a conserved C-terminal region epitope (p145, sequence in single letter amino acids: LRRDLDASREAKKQVEKALE) of the M protein of GAS were isolated from human patients by affinity chromatography and were shown to be of the immunoglobulin G1 (IgG1) and IgG3 subclasses. These antibodies could reduce the number of colonies of serotype 5 GAS in an in vitro opsonization assay by 71-92%, compared with an equal amount of IgG from control adult donors living in non-endemic areas and without antibodies to p145. Addition of the peptide, p145, completely inhibited this opsonization. Indirect immunofluorescence showed that p145-specific antibodies were capable of binding to the surface of M5 GAS whereas control IgG did not. Using chimeric peptides, which contain overlapping segments of p145, each 12 amino acids in length, inserted into a known helical peptide derived from the DNA binding protein of yeast, GCN4, we have been able to further define two minimal regions within p145, referred to as pJ2 and pJ7. These peptides, pJ2 and pJ7, were able to inhibit opsonization by p145 specific antibodies. Finally, we have observed an association between the age-related development of immunity to GAS and the acquisition of antibodies to the conserved epitope, p145, raising the possibility of using this epitope as a target in a prophylactic vaccine administered during early childhood.

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Selected References

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  1. Beachey E. H., Cunningham M. Type-specific inhibition of preopsonization versus immunoprecipitation by Streptococcal M proteins. Infect Immun. 1973 Jul;8(1):19–24. doi: 10.1128/iai.8.1.19-24.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beachey E. H., Seyer J. M., Dale J. B. Protective immunogenicity and T lymphocyte specificity of a trivalent hybrid peptide containing NH2-terminal sequences of types 5, 6, and 24 M proteins synthesized in tandem. J Exp Med. 1987 Sep 1;166(3):647–656. doi: 10.1084/jem.166.3.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bessen D., Fischetti V. A. Influence of intranasal immunization with synthetic peptides corresponding to conserved epitopes of M protein on mucosal colonization by group A streptococci. Infect Immun. 1988 Oct;56(10):2666–2672. doi: 10.1128/iai.56.10.2666-2672.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bessen D., Fischetti V. A. Synthetic peptide vaccine against mucosal colonization by group A streptococci. I. Protection against a heterologous M serotype with shared C repeat region epitopes. J Immunol. 1990 Aug 15;145(4):1251–1256. [PubMed] [Google Scholar]
  5. Boackle R. The complement system. Immunol Ser. 1993;58:135–159. [PubMed] [Google Scholar]
  6. Brennan R. E., Patel M. S. Acute rheumatic fever and rheumatic heart disease in a rural central Australian aboriginal community. Med J Aust. 1990 Sep 17;153(6):335, 338-9. doi: 10.5694/j.1326-5377.1990.tb136942.x. [DOI] [PubMed] [Google Scholar]
  7. Bronze M. S., Courtney H. S., Dale J. B. Epitopes of group A streptococcal M protein that evoke cross-protective local immune responses. J Immunol. 1992 Feb 1;148(3):888–893. [PubMed] [Google Scholar]
  8. Butz S., Rawer S., Rapp W., Birsner U. Immunization and affinity purification of antibodies using resin-immobilized lysine-branched synthetic peptides. Pept Res. 1994 Jan-Feb;7(1):20–23. [PubMed] [Google Scholar]
  9. Currie B. Medicine in tropical Australia. Med J Aust. 1993 May 3;158(9):609, 612-5. doi: 10.5694/j.1326-5377.1993.tb137630.x. [DOI] [PubMed] [Google Scholar]
  10. Dale J. B., Chiang E. Y., Lederer J. W. Recombinant tetravalent group A streptococcal M protein vaccine. J Immunol. 1993 Aug 15;151(4):2188–2194. [PubMed] [Google Scholar]
  11. Fischetti V. A., Bessen D. E., Schneewind O., Hruby D. E. Protection against streptococcal pharyngeal colonization with vaccines composed of M protein conserved regions. Adv Exp Med Biol. 1991;303:159–167. doi: 10.1007/978-1-4684-6000-1_17. [DOI] [PubMed] [Google Scholar]
  12. Fischetti V. A., Bessen D. E., Schneewind O., Hruby D. E. Protection against streptococcal pharyngeal colonization with vaccines composed of M protein conserved regions. Adv Exp Med Biol. 1991;303:159–167. doi: 10.1007/978-1-4684-6000-1_17. [DOI] [PubMed] [Google Scholar]
  13. Jones K. F., Manjula B. N., Johnston K. H., Hollingshead S. K., Scott J. R., Fischetti V. A. Location of variable and conserved epitopes among the multiple serotypes of streptococcal M protein. J Exp Med. 1985 Mar 1;161(3):623–628. doi: 10.1084/jem.161.3.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kemeny E., Grieve T., Marcus R., Sareli P., Zabriskie J. B. Identification of mononuclear cells and T cell subsets in rheumatic valvulitis. Clin Immunol Immunopathol. 1989 Aug;52(2):225–237. doi: 10.1016/0090-1229(89)90174-8. [DOI] [PubMed] [Google Scholar]
  15. LANCEFIELD R. C. Differentiation of group A streptococci with a common R antigen into three serological types, with special reference to the bactericidal test. J Exp Med. 1957 Oct 1;106(4):525–544. doi: 10.1084/jem.106.4.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Miller L. H., Good M. F., Milon G. Malaria pathogenesis. Science. 1994 Jun 24;264(5167):1878–1883. doi: 10.1126/science.8009217. [DOI] [PubMed] [Google Scholar]
  17. O'Connor S. P., Darip D., Fraley K., Nelson C. M., Kaplan E. L., Cleary P. P. The human antibody response to streptococcal C5a peptidase. J Infect Dis. 1991 Jan;163(1):109–116. doi: 10.1093/infdis/163.1.109. [DOI] [PubMed] [Google Scholar]
  18. Pruksakorn S., Currie B., Brandt E., Martin D., Galbraith A., Phornphutkul C., Hunsakunachai S., Manmontri A., Good M. F. Towards a vaccine for rheumatic fever: identification of a conserved target epitope on M protein of group A streptococci. Lancet. 1994 Sep 3;344(8923):639–642. doi: 10.1016/s0140-6736(94)92083-4. [DOI] [PubMed] [Google Scholar]
  19. Pruksakorn S., Currie B., Brandt E., Phornphutkul C., Hunsakunachai S., Manmontri A., Robinson J. H., Kehoe M. A., Galbraith A., Good M. F. Identification of T cell autoepitopes that cross-react with the C-terminal segment of the M protein of group A streptococci. Int Immunol. 1994 Aug;6(8):1235–1244. doi: 10.1093/intimm/6.8.1235. [DOI] [PubMed] [Google Scholar]
  20. Pruksakorn S., Galbraith A., Houghten R. A., Good M. F. Conserved T and B cell epitopes on the M protein of group A streptococci. Induction of bactericidal antibodies. J Immunol. 1992 Oct 15;149(8):2729–2735. [PubMed] [Google Scholar]
  21. Quinn R. W., Vander Zwaag R., Lowry P. N. Acquisition of group A streptococcal M protein antibodies. Pediatr Infect Dis. 1985 Jul-Aug;4(4):374–378. doi: 10.1097/00006454-198507000-00008. [DOI] [PubMed] [Google Scholar]
  22. Somlyo A. V., Bond M., Somlyo A. P., Scarpa A. Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5231–5235. doi: 10.1073/pnas.82.15.5231. [DOI] [PMC free article] [PubMed] [Google Scholar]

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