Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Subunit vaccine design against pathogens causing atherosclerosis
Infections by opportunistic bacteria have significant contributions to morbidity and mortalityin humans. Atherosclerosis is a chronic inflammatory disease characterized by the formation of plaques inside arteries, leading to stroke in humans. In this scenario, recent literature evidences illustrated that atherosclerosis is caused by Gram-negative bacteria such as Chlamydophila pneumoniae, Poryphromonas gingivalis and Helicobacter pylori. The unavailability of common vaccine candidate for the three pathogens causing atherosclerosis has aimed at the identification of potential vaccine candidates against the atherosclerosis infections. In the present study proteomes of three pathogens were compared and identified one common surface exposed protein, UvrA system protein A as common vaccine candidate. UvrA protein was also reported as vaccine candidate in E. coli (Grossman et al., 1997). Nine T-cell epitopes were predicted for UvrA protein using ProPred server by choosing most predominant five HLA-DRB alleles (HLA-DRB1*0101, HLA-DRB1*0301, HLA-DRB1*0401, HLA-DRB1*1501 and HLA-DRB5*0101), further validated with SYFPEITHI and immune epitope database (Munikumar et al., 2013). The T-cell epitope 13-VRNLKNVSI-21of UvrA protein was conserved in the three selected pathogens (Fig 1). Epitope 13-VRNLKNVSI-21 with ProPred score of 37.976 had better binding affinity towards HLA-DRBs than the positive control (32.815) (Priyadarshini et al., 2013) was selected among the nine epitopes (Fig 2). The eleven crystal structures of five HLA-DRB alleles were retrieved from the protein data bank and homology modeling of UvrA protein was performed using Modeller 9v14. The HLA-DRB5*0101-epitope docking complex showed the highest binding affinity and the least negative score of -9.845 kcal/mol (Fig 3). Molecular dynamics simulations were carried out to check the stability of HLA-DRB-epitope complex using Desmond v3.4. The docking and simulations studies revealed that HLA-DRB-epitope complex was stable and the epitope 13-VRNLKNVSI-21 of UvrA protein was identified as common vaccine candidate against the pathogenesis of atherosclerosis.
I highly acknowledge DST, Govt. of India, for providing JRF (NO.DST/INSIRE Fellowship/2012/627). The authors are thankful to DBT, Ministry of Science and Technology, Govt. of India for providing all facilities to carry out the work at SVIMS Bioinformatics centre (BT/BI/04/055/2001, 22nd Sep 2006).
M. Munikumar, I.V. Priyadarshini, D. Pradhan, S. Swargam and A. Umamaheswari. (2013). T-cell vaccine design for Streptococcus pneumoniae: an in silico approach. Journal of Biomolecular Structure and Dynamics 31,114-115.
I.V. Priyadarshini, D. Pradhan, M. Munikumar, S. Swargam, A. Umamaheswari and D. Rajasekhar. (2014). Genome-based approaches to develop epitope-driven subunit vaccines against pathogens of infective endocarditis. Journal of Bimolecular Structure and Dynamics, DOI:10.1080/07391102.2013.79587.