EPITOPE PREDICTION AND STRUCTURAL ANALYSIS OF PRA ANTIGEN OF COCCIDIOIDES

  • Prashant Saxena Department of Bioinformatics, Sathyabama University,Chennai 119, India.
  • Jemmy Christy Department of Bioinformatics, Sathyabama University,Chennai 119, India.

Abstract

Objective: Coccidioidomycosis is a life threatening human respiratory disease caused by Coccidioides immitis and C. posadasii. As the incidence of symptomatic Coccidioidomycosis increases worldwide, vaccine development strategy against Coccidioides is needed for both immunocompetent and immunocompromized individuals. An insight about PRA antigens in the pathogenesis of Coccidioidomycosis has the potential to develop a therapeutic intervention.

Methods: In this study of ANN, SMM and QM based servers were used to predict promiscuous epitopes. Epitope structures were modeled using De novo based PEPFOLD server and minimized using Swiss model server. Further the modeled epitopes were tested for their binding affinity towards HLA alleles by means of peptide protein docking studies involving autodock.

Results: A total of six antigenic epitopes ARISVSNIV, GRPTASTPA, ALNLFVEAL, LVAAGLASA, FSHALJALV, AEPTHEPTE of PRA showed hydrogen bonding with HLA alleles HLA-A*02:03, HLA B*27:05, HLA-A*02:01 with considerable bond distance. Thus, this systematic study on epitopes of Coccidioides study would be helpful in designing and developing novel PRA antigen based vaccine and inhibitor.

Conclusion: These predicted sequences are potential vaccine candidates but functional/biological assays should be performed to verify whether they are indeed appropriate to be included in a vaccine formulation.

 

Keywords: HLA-A*02, 03, HLA-B*27, 05, 01, PRA antigen, Epitope, Coccidioidomycosis, Vaccine.

Downloads

Download data is not yet available.

References

1. Fisher F, Bultman MW, Pappagianis D, Washington DC. Operational Guidelines for Geological Fieldwork in Areas Endemic for Coccidioidomycosis (Valley Fever);US Geological Survey Open-File Report; US Department of the Interior: USA 2000;1-16.
2. Stevens DA. Coccidioidomycosis. The New England J of Medicine 1995;332(16):1077-82.
3. Chiller TM, Galgiani JN, Stevens DA. Coccidioidomycosis. J Infect Dis Clin North Am 2003;17(1):41-57.
4. Saubolle MA, McKellar PP, Sussland D. Epidemiologic, clinical, and diagnostic aspects of coccidioidomycosis. J Clin Microbiol 2007;45(1):26-30.
5. Blair JE. Coccidioidomycosis in patients who have undergone transplantation. J Ann NY Acad Sci 2007;1111:365-76.
6. Kirkland TN, Fierer J. Coccidioidomycosis: a reemerging infectious disease. J Emerg Infect Dis 1996;2(3):192-9.
7. Ampel NM. The complex immunology of human coccidioidomycosis. Ann N Y Acad Sci 2007;1111:245-58.
8. Masannat FY, Ampel NM. Coccidioidomycosis in patients with HIV-1 infection in the era of potent antiretroviral therapy. Clin Infect Dis 2010, 50, 1-7.
9. Santelli AC, Blair JE, Roust LR. Coccidioidomycosis in patients with diabetes mellitus. The American J of Medicine 2006;119(11):964-9.
10. Pappagianis D, Lindsay S, Beall S, Williams P. Ethnic background and the clinical course of coccidioidomycosis. Am Rev Resp Dis1979;120:959-61.
11. Abuodeh RO, LF Shubitz, E Siegel, S Snyder, T Peng, KI Orsborn, E Brummer, DA Stevens, JN Galgiani. Resistance to Coccidioides immitis in mice after immunization with recombinant protein or DNA vaccine of a proline-rich antigen. Infect Immun 1999;67:2935-40.
12. Jiang C, Magee DM, Quitugua TN, Cox RA. Genetic vaccination against Coccidioides immitis: comparison of vaccine efficacy of recombinant antigen 2 and antigen 2 cDNA. Infect Immun 1999;67(2):630-5.
13. Kirkland TN, Finley F, Orsborn KI, Galgiani JN. Evaluation of the proline-rich antigen of Coccidioides immitis as a vaccine candidate in mice. Infect Immun 1998;66(8):3519-22.
14. Schneider E, Hajjeh RA, Spiegel RA, Jibson RW, Harp EL, Marshall GA, et al. A coccidioidomycosis outbreak following the Northridge, Calif, earthquake. J of the American Medical Association 1997;277(11):904-8.
15. GCBM Arun, Susumu Goto. Prediction of CTL epitope in silico modeling and functional analysis of cytolethal distending toxin CDT protein of Campylobacter jejuni Notes 92 2014;7.
16. Menchaca L, Rood H, Komerofsky R D. New allele frequency database: http: //www. allelefrequencies. net. Middleton Tissue Antigens 2003:403-7.
17. Taurog JD. The mystery of HLA-B if it isn’t one thing, it’s another. Arthritis Rheum 2007;27:2478-81.
18. Guan P, Hattotuwagama CK, Doytchinova IA, Flower DR. MHCPred 2.0:an updated quantitative T-cell epitope prediction server. Applied Bioinformatics 2006;5(1):55-61.
19. Alexander H, Hans-Georg S, Hermann-Georg K, Stefan HE, I Jörg Hansjörg Christina tter, Peter-M, et al. MAPPP-MHC-Peptide Processing Prediction. Applied Bioinformatics 2003;2(3):155-8.
20. Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, et al. The immune epitope database 2. 0 Nucleic Acids Res 38Database issue; 2010:854-62.
21. Thévenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tufféry P. PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res 2012;40:288-93.
22. TJN. SWISS-MODEL: an automated protein homology-modeling server. Nucleic Acids Res Oxford Univ Press 2003.
23. Webb B, Sali A. Protein structure modeling with MODELLER. Methods in molecular biology (Clifton, NJ) 2014;1137:1-15.
24. Laskowski RA, McArthur MW, Moss DS, Thornton JM J. PROCHECK: a program to check the stereochemical quality of protein structures. Cryst 1993;26:283-91.
25. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4:Automated docking with selective receptor flexibility. J Comput Chem 2009;30(16):2785-91.
26. Sanner MF J. Python: a programming language for software integration and development. Graphics Mod 1999;17(2):57-61.
Statistics
303 Views | 581 Downloads
How to Cite
Saxena, P., and J. Christy. “EPITOPE PREDICTION AND STRUCTURAL ANALYSIS OF PRA ANTIGEN OF COCCIDIOIDES”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 6, no. 9, 1, pp. 238-43, https://innovareacademics.in/journals/index.php/ijpps/article/view/1967.
Section
Original Article(s)