JJo, a Recombinant Dimer of Conformationally Restricted Peptide Elicits Protective Response against Group A Streptococcus (GAS) Isolates from a GAS-Endemic Region

Abstract

A peptide (J14) containing conformationally restricted epitopes from the M protein of group A streptococcus (GAS) is capable of eliciting protective immune response against GAS infection. However, the protective response may be lost possibly due to its weak secondary-structure when the antigen is fused with other antigens in a recombinant polyepitope vaccine construct. We previously showed that JJo, a conformationally stabilized derivative of dimeric J14, overcomes this problem. We now show that anti JJo antibodies react with diverse GAS isolates found in the Indian sub-continent and that these antibodies are opsonic for GAS. The GAS strains used in this study were isolated from throat and skin swabs from Mumbai, Chennai and Vellore. Sera from mice immunized with recombinant JJo peptide were tested by ELISA, immunofluorescence, flow-cytometry, indirect bactericidal assay and mouse challenge assays to determine specific immunogenicity, opsonic functions and protection against an Indian isolate. We propose that JJo is a robust antigen suitable for inclusion in recombinant multi-epitope vaccines which are potentially affordable option for the pediatric population of developing countries.

Share and Cite:

R. Sunagar, V. Ramachandran, M. Georgousakis, K. Sriprakash and M. Shaila, "JJo, a Recombinant Dimer of Conformationally Restricted Peptide Elicits Protective Response against Group A Streptococcus (GAS) Isolates from a GAS-Endemic Region," World Journal of Vaccines, Vol. 1 No. 4, 2011, pp. 131-137. doi: 10.4236/wjv.2011.14013.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] A. L. Bisno, “Group A Streptococcal Infections and Acute Rheumatic Fever,” New England Journal of Medicine, Vol. 325, No. 11, 1991, pp. 783-793. doi:10.1056/NEJM199109123251106
[2] S. Padmavati, “Rheumatic Fever and Rheumatic Heart Disease in India at the Turn of the Century,” Indian Heart Journal, Vol. 53, 2001, pp. 35-37.
[3] A. Shet and E. Kaplan, “Addressing the Burden of Group A Streptococcal Disease in India,” Indian Journal of Paediatrics, Vol. 71, No. 1, 2004, pp. 41-48. doi:10.1007/BF02725655
[4] J. H. Robinson and M. A. Kehoe, “Group A Streptococcal M Proteins: Virulence Factors and Protective Antigens,” Immunology Today, Vol. 13, No. 9, 1992, pp. 362-367. doi:10.1016/0167-5699(92)90173-5
[5] V. A. Fischetti, “Streptococcal M Protein,” Scientific American, Vol. 264, No. 6, 1991, pp.58-65. doi:10.1038/scientificamerican0691-58
[6] W. A. Hayman, E. R. Brandt, W. A. Relf, J. Cooper, A. Saul and M. F. Good, “Mapping the Minimal Murine T cell and B Cell Epitopes within a Peptide Vaccine Candidate from the Conserved Region of the M Protein of Group A Streptococcus,” International Immunology, Vol. 9, No. 11, 1997, pp. 1723-1733. doi:10.1093/intimm/9.11.1723
[7] S. Pruksakorn, A. Galbraith, R. A. Hougusten and M. F. Good, “Conserved T and B Cell Epitopes on the M Protein of Group A Streptococci. Induction of Bactericidal Antibodies”, The Journal of Immunology, Vol. 149, 1992, pp. 2729-2735.
[8] M. R. Batzloff, W. A. Hayman,M. R. Davies, M. Zeng, S.Pruksakorn, E. R. Brandt, M. F. Good, “Protection against Group A Streptococcus by Immunization with J8-Diphtheria Toxoid: Contribution of J8- and Diphtheria Toxoid-Specific Antibodies to Protection,” The Journal of Infectious Diseases, Vol. 187, No. 10, 2003, pp. 1598- 1608. doi:10.1086/374800
[9] H. Vohra, N. Dey, S. Gupta, A. K. Sharma, R. Kumar, D. J. McMillan and M. F. Good, “M Protein Conserved Region Antibodies Opsonise Multiple Strains of Streptococcus Pyogenes with Sequence Variations in C-Repeats,” Research in Microbiology, Vol. 156, No. 4, 2005, pp. 575-582. doi:10.1016/j.resmic.2004.12.009
[10] M. M. Georgousakis, A. Hofmann, M. R. Batzloff, D. J. McMillan and K. S. Sriprakash, “Structural Optimisation of a Conformational Epitope Improves Antigenicity When Expressed as a Recombinant Fusion Protein,” Vaccine, Vol. 27, No. 48, 2009, pp. 6799-6806. doi:10.1016/j.vaccine.2009.08.049
[11] T. A. Penfound, E. Y. Chiang, E. A. Ahmed and J. B. Dale, “Protective Efficacy of Group A Streptococcal Vaccines Containing Type-Specific and Conserved M Protein Epitopes,” Vaccine, Vol. 28, No. 31, 2010, pp. 5017-5022. doi:10.1016/j.vaccine.2010.05.018
[12] B. Beall, R. Facklam and T. Thompson, “Sequencing Emm-Specific PCR Products for Routine and Accurate Typing of Group A Streptococci,” Journal of Clinical Microbiology, Vol. 34, 1996, pp. 953-958.
[13] E. R. Brandit, K. S. Sriprakash, R. I. Hobb, W. A. Hayman, W. Zeng, M. R. Batzloff, D. C. Jackson and M. F. Good, “New Multi-Determinant Strategy for a Group A Streptococcal Vaccine Designed for the Australian Aboriginal Population,” Nature Medicine, Vol. 6, No. 4, 2000, pp. 455-459.
[14] M. G. Caparon, R. T. Geist, J. Perez-Casal and J. R. Scott, “Environmental Regulation of Virulence in Group A Streptococci: Transcription of the Gene Encoding M Protein Is Stimulated by Carbon Dioxide,” Journal of Bacteriology, Vol. 174, 1992, pp. 5693-5701.
[15] H. S. Courtney, O. I. Penfound, T. V. Nizet, M. A. Pence, B. Kreikemeyer, A. Podbielski, D. L. Hasty and J. B. Dale, “Relationship between Expression of the Family of M Proteins and Lipoteichoic Acid to Hydrophobicity and Biofilm Formation in Streptococcus Pyogenes,” PLoS One, Vol. 4, No. 1, 2009, p. e4166. doi:10.1371/journal.pone.0004166
[16] M. R. Batzloff, H. Yan, M. R. Davies, J. Hartas, G. H. Lowell, G. White, D. S. Burt, T. Leanderson and M. F. Good, “Toward the Development of an Antidisease, Transmission-Blocking Intranasal Vaccine for Group A Streptococcus,” The Journal of Infectious Diseases, Vol. 192, No. 8, 2005, pp. 1450-1455. doi:10.1086/466528
[17] G. Stollerman, F. Kantor and B. Gordon, “Accessory Plasma Factors Involved in the Bactericidal Test for Type-Specific Antibody to Group A Streptococci. I. Atypical Behavior of Some Human and Animal Bloods,” Journal of Experimental Medicine, Vol. 108, 1958, pp. 475-491. doi:10.1084/jem.108.4.475
[18] A. C. Steer, G. Magor, A. W. J. Jenney, J. Kado, M. F. Good, D. J. McMillan, M. Batzloff and J. R. Carapetis “Emm and C-Repeat Region Molecular Typing of Beta- Hemolytic Streptococci in a Tropical Country: Implications for Vaccine Development,” Journal of Clinical, Microbiology, Vol. 47, No. 8, 2009, pp. 2502-2509. doi:10.1128/JCM.00312-09
[19] N. Yoonim, C. Olive, C. Pruksachatkunakorn and S. Pruksakorn, “Bactericidal Activity of M Protein Conserved Region Antibodies against Group A Streptococcal Isolates from the Northern Thai Population,” BMC Microbiology, Vol. 6, 2006, p. 71.
[20] J. C. Levin and M. R. Wessels, “Identification of csrR/ csrS, a Genetic Locus That Regulates Hylarunic Acid Capsule Synthesis in Group A Streptococcus,” Molecular Microbiology, Vol. 30, No. 1, 1998, pp. 209-219.
[21] P. R. Smeesters, D. J. McMillan and K. S. Sriprakash, “The Streptococcal M Protein: A Highly Versatile Molecule,” Trends in Microbiology, Vol. 18, No. 6, 2010, pp. 275-282. doi:10.1016/j.tim.2010.02.007
[22] W. J. Simpson and P. P. Cleary, “Expression of M Type 12 Protein by a Group A Streptococcus Exhibits Phaselike Variation: Evidence for Coregulation of Colony Opacity Determinants and M Protein,” Infection and Immunity, Vol. 55, No. 10, 1987, pp. 2448-2455.
[23] S. P. O’Connor and P. P. Cleary, “In Vivo Streptococcus Pyogenes C5a Peptidase Activity: Analysis Using Trans- poson- and Nitrosoguanidine-Induced Mutants,” The Journal of Infectious Diseases, Vol. 156, No. 3, 1987, pp. 495-504. doi:10.1093/infdis/156.3.495
[24] W. A. Relf, J. Cooper, E. R. Brandt, W. A. Hayman, R. F. Anders, S. Pruksakorn, B. Currie, A. Saul and M. F. Good, “Mapping a Conserved Conformational Epitope from the M Protein of Group A Streptococci,” Peptide Research, Vol. 9, 1996, pp. 12-20.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.