IN SILICO APPROACH FOR FUTURE DEVELOPMENT OF SUBUNIT VACCINES AGAINST LEPTOSPIRA INTERROGANS SEROVAR LAI

Rakesh S.1, Pradhan D.2, Umamaheswari A.3*
1SVIMS Bioinformatics Centre, Department of Bioinformatics, SVIMS University, Tirupati, A.P., India – 517 507.
2SVIMS Bioinformatics Centre, Department of Bioinformatics, SVIMS University, Tirupati, A.P., India – 517 507.
3SVIMS Bioinformatics Centre, Department of Bioinformatics, SVIMS University, Tirupati, A.P., India – 517 507.
* Corresponding Author : amineni.maheswari@gmail.com

Received : -     Accepted : -     Published : 21-12-2009
Volume : 1     Issue : 2       Pages : 85 - 92
Int J Bioinformatics Res 1.2 (2009):85-92
DOI : http://dx.doi.org/10.9735/0975-3087.1.2.85-92

Keywords : Leptospirosis, reverse vaccinology, subunit vaccine, HLA DRB1, T-Cell epitopes
Conflict of Interest : None declared

Cite - MLA : Rakesh S., et al "IN SILICO APPROACH FOR FUTURE DEVELOPMENT OF SUBUNIT VACCINES AGAINST LEPTOSPIRA INTERROGANS SEROVAR LAI." International Journal of Bioinformatics Research 1.2 (2009):85-92. http://dx.doi.org/10.9735/0975-3087.1.2.85-92

Cite - APA : Rakesh S., Pradhan D. , Umamaheswari A. (2009). IN SILICO APPROACH FOR FUTURE DEVELOPMENT OF SUBUNIT VACCINES AGAINST LEPTOSPIRA INTERROGANS SEROVAR LAI. International Journal of Bioinformatics Research, 1 (2), 85-92. http://dx.doi.org/10.9735/0975-3087.1.2.85-92

Cite - Chicago : Rakesh S., Pradhan D. , and Umamaheswari A. "IN SILICO APPROACH FOR FUTURE DEVELOPMENT OF SUBUNIT VACCINES AGAINST LEPTOSPIRA INTERROGANS SEROVAR LAI." International Journal of Bioinformatics Research 1, no. 2 (2009):85-92. http://dx.doi.org/10.9735/0975-3087.1.2.85-92

Copyright : © 2009, Rakesh S., et al, Published by Bioinfo Publications. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Abstract

Leptospirosis continues to have major impacts on people of developing countries with inestimable morbidity and mortality. As current leptospirosis vaccination is relatively unsuccessful, development of efficacious vaccines through novel means became utmost priority for prevention of frequent outbreaks of the disease. Herein, MHC class II restricted peptide epitopes were identified from pathogenic Leptospiral membrane proteins to suggest T-cell epitope driven leptospirosis vaccines through reverse vaccinology. The proteome of Leptospira interrogans serovar Lai was screened to select 137 membrane proteins. Jemboss Antigenic server was employed to find antigenic peptides, followed by ProPred analysis to predict 30 short peptides having strong binding affinity with HLA DRB1*0101, DRB1*0401 and DRB1*1501 alleles. Predictions were revised to pick antigenic peptides with same core region binding with the selected HLADRB1 alleles and ten such peptides were found from seven proteins. Further, to confirm the interaction at structure level, Leptospira excinuclease ABC subunit B protein having short T-cell antigenic peptide (133-REDVVIVSSVSCIYGLG-149) was modeled using Modeller9v7. The model reliability was evaluated through Procheck, ProSA and ProQ. Docking calculations for selected HLA DRB1 alleles (receptor) and modelled Leptospira excinuclease ABC subunit B protein (ligand) were carried out using Hex 5.1. The protein –protein interaction revealed that the core region (136-VVIVSSVSC-144) of the antigenic peptide (133-REDVVIVSSVSCIYGLG-149) was well interacting with the receptors. Through the reverse vaccinology approach and docking studies, the short antigenic peptide 133-REDVVIVSSVSCIYGLG-149 of Leptospira excinuclease ABC subunit B is proposed as a potential novel T-cell driven subunit vaccine against leptospirosis.

References

[1] Levett P.N. (2001) Clinical Microbiology Reviews, 14(2), 296-326  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[2] Wang Z., Jin L. and Wegrzyn A. (2007) Microbial Cell Factories, 6, 39  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[3] Faine S.B., Adler B., Bolin C. and Perolat P. (1999) Medisci, Melbourne, Australia, 2nd edition, 193-199  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[4] Farr R.W. (1995) Clinical Infectious Diseases, 21(1), 1-6.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[5] Romero E.C., Bernardo C.C. and Yasuda P.H. (2003) Rev Inst Med Trop Sao Paulo, 45(5), 245-248  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[6] Trueba G., Zapata S., Madrid K., Cullen P. and Haake D. (2004) International Microbiology, 7(1), 35-40  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[7] Cacciapuoti B., Vellucci A., Ciceroni L., Pinto A. and Taggi F. (1987) European Journal of Epidemiology, 3(2), 137-142  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[8] Everard C.O.R., Haynes R.J. and Edwards C.N. (1989) Epidemiology and Infection, 103(1), 143-156.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[9] Serruto D., Serino L., Masignani V. and Pizza M. (2009) Vaccine, 27(25-26), 3245-3250  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[10] Rappuoli R. (2001) Vaccine, 19(17-19), 2688- 2691  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[11] Petrovsky N., Schonbach C. and Brusic V. (2003) In Silico Biology, 3(4), 411-416  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[12] Barker C.J., Beagley K.W., Hafner L.M. and Timms P. (2008) Vaccine, 26(10), 1285- 1296  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[13] De Groot A.S., McMurry J., Marcon L., Franco J., Rivera D., Kutzler M., Weiner D. and Martin B. (2005) Vaccine, 23(17-18), 2121- 2131.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[14] Panigada M., Sturniolo T., Besozzi G., Boccieri M.G., Sinigaglia F., Grassi G.G. and Grassi F. (2002) Infection and immunity, 70(1), 79-85.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[15] De Groot A.S., Bosma A., Chinai N., Frost J., Jesdale B.M., Gonzalez M.A., Martin W. and Aubin C.S. (2001) Vaccine, 19 (31), 4385-4395  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[16] Ren S.X., Fu G., Jiang X.G., Zeng R., Miao Y.G., Xu H., Zhang Y.X., Xiong H., Lu G., Lu L.F., Jiang H.Q., Jia J., Tu Y.F., Jiang J.X., Gu W.Y., Zhang Y.Q., Cai Z., Sheng H.H., Yin H.F., Zhang Y., Zhu G.F., Wan M., Huang H.L., Qian Z., Wang S.Y., Ma W., Yao Z.J., Shen Y., Qiang B.Q., Xia Q.C., Guo X.K., Danchin A., Girons I.S., Somerville R.L., Wen Y.M., Shi M.H., Chen Z., Xu J.G. and Zhao G.P. (2003) Nature, 422(6934), 888-893  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[17] Nascimento A.L., Verjovski-Almeida S., Van Sluys M.A., Monteiro-Vitorello C.B., Camargo L.E., Digiampietri L.A., Harstkeerl R.A., Ho P.L., Marques M.V., Oliveira M.C., Setubal J.C., Haake D.A. and Martins E.A. (2004) Brazilian Journal of Medical and Biological Research, 37(4), 459-477.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[18] Bulach D.M., Zuerner R.L., Wilson P., Seemann T., McGrath A., Cullen P.A., Davis J., Johnson M., Kuczek E., Alt D.P., Peterson-Burch B., Coppel R.L., Rood J.I., Davies J.K. and Adler B. (2006) PNAS,103(39), 14560-14565  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[19] Gebriel A.M., Subramaniam G. and Sekaran S.D. (2006) Tropical Biomedicine, 23(2), 194–207  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[20] Jenkins M.K., Khoruts A., Ingulli E., Mueller D.L., McSorley S.J., Reinhardt R.L., Itano A. and Pape K.A. (2001) Annual Review of Immunology, 19, 23–45  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[21] Kuhns J.J, Batalia M.A, Yan S. and Collins E.J. (1999) Journal of biological chemistry, 274(51), 36422-36427  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[22] Kuhns J.J, Batalia M.A, Yan S. and Collins E.J. (1999) Journal of biological chemistry, 274(51), 36422-36427  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[23] Watts C. (1997) Annual Review of Immunology, 15, 821–850  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[24] Chicz R.M., Urban R.G., Lane W.S., Gorga J.C., Stern L.J., Vignali D.A. and Strominger J. L. (1992) Nature, 358, (6389), 764–768.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[25] Rudensky A., Hurlburt P.P., Hong S.C., Barlow A. and Janeway C.A. (1991) Nature, 353 (6345), 622–627  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[26] Rudolph M.G. and Wilson I.A. (2002) Current Opinion in Immunology, 14(1), 52–65.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[27] Serruto D. and Rappuoli R. (2006) FEBS Letters, 580(12), 2985-2992  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[28] Carver T. and Bleasby A. (2003) Bioinformatics, 19(14), 1837-1843.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[29] Kolaskar A.S. and Tongaonkar P.C. (1990) FEBS Letters, 276(1-2), 172-174.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[30] Singh H. and Raghava G.P.S. (2001) Bioinformatics, 17(12), 1236-1237  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[31] Sturniolo T., Bono E., Ding J., Raddrizzani L., Tuereci O., Sahin U., Braxenthaler M., Gallazzi F., Protti M.P., Sinigaglia F. and Hammer J. (1999) Nature Biotechnology, 17(6), 555-561  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[32] Altschul S.F., Madden T.L., Schaffer A.A., Zhang J., Zhang Z., Miller W. and Lipman D.J. (1997) Nucleic Acids Research, 25(17), 3389–3402  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[33] Berman H.L., Westbrook J., Feng Z., Gilliland G., Bhat T.N., Weissig H., Shindyalov I.N. and Bourne P. E. (2000) Nucleic Acids Research, 28(1), 235-242  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[34] Thompson J.D., Gibson T.J., Plewniak F., Jeanmougin F. and Higgins D.G. (1997) Nucleic Acids Research, 25(24), 4876– 4882  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[35] Sali A. and Blundell T.L. (1993) Journal of Molecular Biology, 234(3), 779-815  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[36] Laskowski R.A., MacArthur M.W., Moss D.S. and Thornton J. M. (1993) Journal of Applied Crystallography, 26(2), 283-291  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[37] Wiederstein M. and Sippl M.J. (2007) Nucleic Acids Research, 35, 407-410  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[38] Wallner B. and Elofsson A. (2003) Protein Science, 12(5), 1073-1086  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[39] Castrignano T., De Meo P.D.O., Cozzetto D., Talamo I.G. and Tramontano A. (2006) Nucleic Acids Research, 34, 306–309  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[40] Ritchie D.W., Kozakov D. and Vajda S. (2008) Bioinformatics, 24(17), 1865-1873.  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus  

[41] Bryson K., McGuffin L.J., Marsden R.L., Ward J.J., Sodhi, J.S. and Jones, D.T. (2005) Nucleic Acids Research, 33, 36-38  
» CrossRef   » Google Scholar   » PubMed   » DOAJ   » CAS   » Scopus