Skip to main content

Advertisement

SpringerLink
Log in

The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Schistosomiasis remains an important parasitic disease that affects millions of individuals worldwide. Despite the availability of chemotherapy, the occurrence of constant reinfection demonstrates the need for additional forms of intervention and the development of a vaccine represents a relevant strategy to control this disease. With the advent of genomics and bioinformatics, new strategies to search for vaccine targets have been proposed, as the reverse vaccinology. In this work, computational analyses of Schistosoma mansoni membrane proteins were performed to predict epitopes with high affinity for different human leukocyte antigen (HLA)-DRB1. Ten epitopes were selected and along with murine major histocompatibility complex (MHC) class II molecule had their three-dimensional structures optimized. Epitope interactions were evaluated against murine MHC class II molecule through molecular docking, electrostatic potential, and molecular volume. The epitope Sm141290 and Sm050890 stood out in most of the molecular modeling analyses. Cellular proliferation assay was performed to evaluate the ability of these epitopes to bind to murine MHC II molecules and stimulate CD4+ T cells showing that the same epitopes were able to significantly stimulate cell proliferation. This work showed an important strategy of peptide selection for epitope-based vaccine design, achieved by in silico analyses that can precede in vivo and in vitro experiments, avoiding excessive experimentation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. WHO (2010). Schistosomiasis. Fact sheet no 115. WHO Media centre: World Health Organization.

  2. Secor, W. E. (2014). Water-based interventions for schistosomiasis control. Pathogens and Global Health, 108(5), 246–254.

    Article  Google Scholar 

  3. King, C. H., Olbrych, S. K., Soon, M., Singer, M. E., Carter, J., & Colley, D. G. (2011). Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review. PLoS Neglected Tropical Diseases, 5, 1–15.

    Google Scholar 

  4. Sabra, A. N., & Botros, S. S. (2008). Response of Schistosoma mansoni isolates having different drug sensitivity to praziquantel over several life cycle passages with and without therapeutic pressure. Journal of Parasitology, 94, 537–541.

    Article  Google Scholar 

  5. Oliveira, S. C., Fonseca, C. T., Cardoso, F. C., Farias, L. P., & Leite, L. C. (2008). Recent advances in vaccine research against schistosomiasis in Brazil. Acta Tropica, 108, 256–262.

    Article  CAS  Google Scholar 

  6. Souza, C. P., Araújo, N., Jannotti, L. K., & Gazzinelli, G. (1987). Factors that might affect the creation and maintenance of infected snails and the production of Schistosoma mansoni cercariae. Memórias do Instituto Oswaldo Cruz, 82, 73–79.

    Article  Google Scholar 

  7. McManus, D. P., & Loukas, A. (2008). Current status of vaccines for schistosomiasis. Clinical Microbiology Reviews, 21(1), 225–242.

    Article  CAS  Google Scholar 

  8. Bethony, J. M., Cole, R. N., Guo, X., Kamhawi, S., Lightowlers, M. W., Loukas, A., et al. (2011). Vaccines to combat the neglected tropical diseases. Immunological Reviews, 239(1), 237–270.

    Article  CAS  Google Scholar 

  9. Fonseca, C. T., Oliveira, S. C., & Alves, C. C. (2015). Eliminating Schistosomes through vaccination: what are the best immune weapons? Frontiers in Immunology, 9, 6–95.

    Google Scholar 

  10. Bergquist, N. R., Leonardo, L. R., & Mitchell, G. F. (2005). Vaccine-linked chemotherapy: can schistosomiasis control benefit from an integrated approach? Trends in Parasitology, 21(3), 112–117.

    Article  CAS  Google Scholar 

  11. Artimo, P., Jonnalagedda, M., Arnold, K., Baratin, D., Csardi, G., & de Castro, E., et al. (2012). ExPASy: SIB bioinformatics resource portal. Nucleic Acids Research, 40(Web Server issue), W597–603.

  12. Durmuş, S., Çakır, T., Özgür, A., & Guthke, R. (2015). A review on computational systems biology of pathogen-host interactions. Frontiers in Microbiology, 6, 235.

    Google Scholar 

  13. Lopes, D. O., Oliveira, F. M., Coelho, I. E. V., Santana, K. T. O., Mendonça, F. C., Taranto, A. G., et al. (2013). Identification of a vaccine against schistosomiasis using bioinformatics and molecular modeling tools. Infection, Genetics and Evolution, 20, 83–95.

    Article  CAS  Google Scholar 

  14. Liebenberg, J., Pretorius, A., Faber, F. E., Collins, N. E., Allsopp, B. A., & van Kleef, M. (2012). Identification of Ehrlichia ruminantium proteins that activate cellular immune responses using a reverse vaccinology strategy. Veterinary Immunology and Immunopathology, 145, 340–349.

    Article  CAS  Google Scholar 

  15. Seib, K. L., Zhao, X., & Rappuoli, R. (2012). Developing vaccines in the era of genomics: a decade of reverse vaccinology. Clinical Microbiology and Infection, 5, 109–116.

    Article  Google Scholar 

  16. Cozzi, R., Scarselli, M., & Ferlenghi, I. (2013). Structural vaccinology: a three-dimensional view for vaccine development. Current Topics in Medicinal Chemistry, 13, 2629–2637.

    Article  Google Scholar 

  17. Agudelo, W. A., & Patarroyo, M. E. (2010). Quantum chemical analysis of MHC-peptide interactions for vaccine design. Mini Reviews in Medicinal Chemistry, 10, 746–758.

    Article  CAS  Google Scholar 

  18. Wiens, K. E., Swaminathan, H., Copin, R., Lun, D. S., & Ernst, J. D. (2013). Equivalent T cell epitope promiscuity in ecologically diverse human pathogens. PLoS One, 8(8), e73124.

    Article  CAS  Google Scholar 

  19. Zhu, J., & Paul, W. E. (2008). CD4 T cells: fates, functions, and faults. Blood, 112, 1557–1569.

    Article  CAS  Google Scholar 

  20. Zhao, B., Sakharkar, K. R., Lim, C. S., Kangueane, P., & Sakharkar, M. K. (2007). MHC-peptide binding prediction for epitope based vaccine design. International Journal of Integrative Biology, 1, 127–140.

    CAS  Google Scholar 

  21. Trott, O., & Olson, A. J. (2010). Software news and update AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31, 455–461.

    CAS  Google Scholar 

  22. Cardoso, F. C., Pacífico, R. N., Mortara, R. A., & Oliveira, S. C. (2006). Human antibody responses of patients living in endemic areas for schistosomiasis to the tegumental protein Sm29 identified through genomic studies. Clinical and Experimental Immunology, 144, 382–391.

    Article  CAS  Google Scholar 

  23. Ribeiro, S. P., Rosa, D. S., Fonseca, S. G., Mairena, E. C., Postól, E., & Oliveira, S. C., et al. (2010). A vaccine encoding conserved promiscuous HIV CD4 epitopes induces broad T cell responses in mice transgenic to multiple common HLA class II molecules. PLOS One, 5(6).

  24. Lopes, D. O., Paiva, L. F., Martins, M. A., Cardoso, F. C., Rajão, M. A., Pinho, J. M., et al. (2009). Sm21.6 a novel EF-hand family protein member located on the surface of Schistosoma mansoni adult worm that failed to induce protection against challenge infection but reduced liver pathology. Vaccine, 27, 4127–4135.

    Article  CAS  Google Scholar 

  25. Texier, C., Pouvelle, S., Busson, M., Hervé, M., Charron, D., Ménez, A., et al. (2000). HLA-DR restricted peptide candidates for bee venom immunotherapy. Journal of Immunology, 164(6), 3177–3184.

    Article  CAS  Google Scholar 

  26. Case, D. A., Darden, T. A., Cheatham, T. E. I. I. I., Simmerling, C. L., Wang, J., Duke, R. E., et al. (2010). AMBER11. San Francisco: University of California.

    Google Scholar 

  27. Hawkins, G. D., Cramer, C. J., & Truhlar, D. G. (1996). Parametrized models of aqueous free energies of solvation based on pairwise descreening of solute atomic charges from a dielectric medium. The Journal of Physical Chemistry, 100, 19824–19839.

    Article  CAS  Google Scholar 

  28. Hawkins, G. D., Cramer, C. J., & Truhlar, D. G. (1995). Pairwise solute descreening of solute charges from a dielectric medium. Chemical Physics Letters, 246, 122–129.

    Article  CAS  Google Scholar 

  29. Duan, Y., Wu, C., Chowdhury, S., Lee, M. C., Xiong, G., Zang, W., et al. (2003). A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculation. Journal of Computational Chemistry, 24, 1999–2012.

    Article  CAS  Google Scholar 

  30. Lee, M. C., & Duan, Y. (2004). Distinguish protein decoys by using a scoring function based a new Amber force field, short molecular dynamics simulations, and the generalized Born solvent model. Proteins, 55, 620–634.

    Article  CAS  Google Scholar 

  31. Dennington, R., Keith, T., & Millam, J. (2009). GaussView, Version 5. Semichem Inc., Shawnee Mission KS.

  32. Nakamura, S., Takahira, K., Tanabe, G., Morikawa, T., Sakano, M., Ninomiya, K., et al. (2010). Docking and SAR studies of salacinol derivatives as α-glucosidase inhibitors. Bioorganic & Medicinal Chemistry Letters, 20, 4420–4423.

    Article  CAS  Google Scholar 

  33. Sanner, M. F. (1999). Python: a programming language for software integration and development. Journal of Molecular Graphics & Modelling, 17, 57–61.

    CAS  Google Scholar 

  34. Enviroment, D. S. M. (2012). Accelrys software inc, release 3.1. San Diego.

  35. Pacífico, L. G., Marinho, F. A., Fonseca, C. T., Barsante, M. M., Pinho, V., Sales-Junior, P. A., et al. (2009). Schistosoma mansoni antigens modulate experimental allergic asthma in a murine model: a major role for CD4+ CD25+ Foxp3+ T cells independent of interleukin-10. Infection and Immunity, 77, 98–107.

    Article  Google Scholar 

  36. Boyaka, P. N., Tafaro, A., Fischer, R., Leppla, S. H., Fujihashi, K., & McGhee, J. R. (2003). Effective mucosal immunity to anthrax: neutralizing antibodies and Th cell responses following nasal immunization with protective antigen. Journal of Immunology, 170(11), 5636–5643.

    Article  CAS  Google Scholar 

  37. Aziz, M., Yang, W. L., Matsuo, S., Sharma, A., Zhou, M., & Wang, P. (2014). Upregulation of GRAIL is associated with impaired CD4 T cell proliferation in sepsis. Journal of Immunology, 192(5), 2305–2314.

    Article  CAS  Google Scholar 

  38. Gasteiger, J., & Marsili, M. (1980). Iterative partial equalization of orbital electronegativity—a rapid access to atomic charges. Tetrahedron, 36, 3219–3228.

    Article  CAS  Google Scholar 

  39. Gasteiger, J., & Marsili, M. (1978). A new model for calculating atomic charges in molecules. Tetrahedron Letters, 19, 3181–3184.

    Article  Google Scholar 

  40. Del Carpio, C. A., Hennig, T., Fickel, S., & Yoshimori, A. (2002). A combined bioinformatic approach oriented to the analysis and design of peptides with high affinity to MHC class I molecules. Immunology and Cell Biology, 80(3), 286–299.

    Article  Google Scholar 

  41. Sette, A., & Rappuoli, R. (2010). Reverse vaccinology: developing vaccines in the era of genomics. Immunity, 33(4), 530–541.

    Article  CAS  Google Scholar 

  42. Pinheiro, C. S., Martins, V. P., Assis, N. R. G., Figueiredo, B. C. P., Morais, S. B., Azevedo, V., et al. (2011). Computational vaccinology: an important strategy to discover new potential S. mansoni vaccine candidates. Journal of Biomedicine & Biotechnology, 2011, 503068.

    Article  Google Scholar 

  43. Zhang, Y. L., Jia, K., Zhao, B. P., Li, Y., Yuan, C. X., Yang, J. M., et al. (2012). Identification of Th1 epitopes within molecules from the lung-stage schistosomulum of Schistosoma japonicum by combining prediction analysis of the transcriptome with experimental validation. Parasitology International, 61, 586–593.

    Article  CAS  Google Scholar 

  44. Chitale, M., Hawkins, T., Park, C., & Kihara, D. (2009). ESG: extended similarity group method for automated protein function prediction. Bioinformatics, 25(14), 1739–4.

    Article  CAS  Google Scholar 

  45. Dahl, G., & Muller, K. J. (2014). Innexin and pannexin channels and their signaling. FEBS Letters, 588(8), 1396–1402.

    Article  CAS  Google Scholar 

  46. Bissantz, C., Kuhn, B., & Stahl, M. (2010). A medicinal chemist’s guide to molecular interactions. Journal of Medicinal Chemistry Perspective, 53(14), 5061–5084.

    Article  CAS  Google Scholar 

  47. Zhu, Y., Rudensky, A. Y., Corper, A. L., Teyton, L., & Wilson, I. A. (2003). Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide: prediction of an I-Ab peptide-binding motif. Journal of Molecular Biology, 326(4), 1157–1174.

    Article  CAS  Google Scholar 

  48. Gilson, M. K., & Honig, B. H. (1987). Calculation of electrostatic potentials in an enzyme active-site. Nature, 330, 84–86.

    Article  CAS  Google Scholar 

  49. Weiner, P. K., Langridge, R., Blaney, J. M., Schaefer, R., & Kollman, P. A. (1982). Electrostatic potential molecular-surfaces. Proceedings of the National Academy of Sciences of the United States of America, 79, 3754–3758.

    Article  CAS  Google Scholar 

  50. Dewar, M. J. S., Zoebisch, E. G., Healy, E. F., & Stewart, J. J. P. (1985). The development and use of quantum mechanical molecular models.76. Am1—a new general purpose quantum mechanical molecular-model. Journal of the American Chemical Society, 107, 3902–3909.

    Article  CAS  Google Scholar 

  51. Halgren, T. A. (1996). Merck molecular force field 3. Molecular geometries and vibrational frequencies for MMFF94. Journal of Computational Chemistry, 17, 553–586.

    Article  CAS  Google Scholar 

  52. Tsai, K. C., Wang, S. H., Hsiao, N. W., Li, M., & Wang, B. (2008). The effect of different electrostatic potentials on docking accuracy: a case study using DOCK5.4. Bioorganic & Medicinal Chemistry Letters, 18, 3509–3512.

    Article  CAS  Google Scholar 

  53. Engelhard, V. H. (1994). Structure of peptides associated with class I and class II MHC molecules. Annual Review of Immunology, 12, 181–207.

    Article  CAS  Google Scholar 

  54. Zhao, B. P., Chena, L., Zhanga, Y. L., Yanga, J. M., Jiaa, K., Sui, C. Y., et al. (2012). In silico prediction of binding of promiscuous peptides to multiple MHC class-II molecules identifies the Th1 cell epitopes from secreted and transmembrane proteins of Schistosoma japonicum in BALB/c mice. Microbes and Infection, 13(7), 709–719.

    Article  Google Scholar 

  55. Cook, P. C., Aynsley, S. A., Turner, J. D., Jenkins, G. R., Van Rooijen, N., Leeto, M., et al. (2011). Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells. PLoS Pathogens, 7, 1–14.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil

    Flávio M. Oliveira, Marcelo D. Lopes, Luciana L. D. Santos, José A. P. F. Villar & Débora D. O. Lopes

  2. Laboratory of Molecular Modeling, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil

    Ivan E. V. Coelho, Alex G. Taranto & Moacyr C. Junior

  3. Research Group in Parasite Biology and Immunology, Centro de Pesquisas René Rachou–Fundação Oswaldo Cruz, Av. Augusto de Lima, Belo Horizonte, MG, 30190-002, Brazil

    Cristina T. Fonseca

Authors
  1. Flávio M. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ivan E. V. Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marcelo D. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alex G. Taranto
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Moacyr C. Junior
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luciana L. D. Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José A. P. F. Villar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Cristina T. Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Débora D. O. Lopes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Débora D. O. Lopes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOC 1923 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oliveira, F.M., Coelho, I.E.V., Lopes, M.D. et al. The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni . Appl Biochem Biotechnol 179, 1023–1040 (2016). https://doi.org/10.1007/s12010-016-2048-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-016-2048-1

Keywords

Search

Navigation