Excavating chikungunya genome to design B and T cell multi-epitope subunit vaccine using comprehensive immunoinformatics approach to control chikungunya infection

被引:63
作者
Narula, Aruna [1 ]
Pandey, Rajan Kumar [1 ]
Khatoon, Nazia [1 ]
Mishra, Amit [2 ]
Prajapati, Vijay Kumar [1 ]
机构
[1] Cent Univ Rajasthan, Sch Life Sci, Dept Biochem, Ajmer 305817, Rajasthan, India
[2] Indian Inst Technol Jodhpur, Cellular & Mol Neurobiol Unit, Jodhpur 342011, Rajasthan, India
关键词
Immunoinformatics; Chikungunya virus; Subunit vaccine; T-cell epitope; B-cell epitope; TOLL-LIKE RECEPTOR-3; TRYPANOTHIONE REDUCTASE; MOLECULAR DOCKING; PEPTIDE VACCINE; FEBRIFUGINE ANALOGS; POTENTIAL INHIBITOR; IMMUNE-RESPONSE; PROTEIN; PREDICTION; ADMET;
D O I
10.1016/j.meegid.2018.03.007
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Chikungunya infection has been a cause of countless deaths worldwide. Due to lack of permanent treatment and prevention of this disease, the mortality rate remains very high. Therefore, we followed an immunoinformatics approach for the development of multi-epitope subunit vaccine which is able to elucidate humoral, cell-mediated and innate immune responses inside the host body. Both structural and non-structural proteins of chikungunya virus were utilized for prediction of B-cell and T-cell binding epitopes along with interferon-gamma (IFN-gamma) inducing epitopes. The vaccine construct is composed of beta-defensin as an adjuvant at the N-terminal followed by Cytotoxic T-Lymphocytes (CTL) and Helper T-Lymphocyte (HTL) epitopes. The same vaccine construct was also utilized for the prediction of B-cell binding epitopes and IFN-gamma inducing epitopes. This was followed by the 3D model generation, refinement and validation of the vaccine construct. Later on, the interaction of modeled vaccine with the innate immune receptor (TLR-3) was explored by performing molecular docking and molecular dynamics simulation studies. Also to check the efficiency of expression of this vaccine construct in an expression vector, in silico cloning was performed at the final stage of vaccine development. Further, designed multi-epitope subunit vaccine necessitates experimental and clinical investigation to develop as an immunogenic vaccine candidate.
引用
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页码:4 / 15
页数:12
相关论文
共 61 条
[1]   Two years into reverse vaccinology [J].
Adu-Bobie, J ;
Capecchi, B ;
Serruto, D ;
Rappuoli, R ;
Pizza, M .
VACCINE, 2003, 21 (7-8) :605-610
[2]   Perturbed microRNA expression by Mycobacterium tuberculosis Promotes Macrophage Polarization leading to Pro-survival Foam cell [J].
Ahluwalia, Pankaj Kumar ;
Pandey, Rajan Kumar ;
Sehajpal, Prabodh Kumar ;
Prajapati, Vijay Kumar .
FRONTIERS IN IMMUNOLOGY, 2017, 8
[3]   A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection [J].
Akahata, Wataru ;
Yang, Zhi-Yong ;
Andersen, Hanne ;
Sun, Siyang ;
Holdaway, Heather A. ;
Kong, Wing-Pui ;
Lewis, Mark G. ;
Higgs, Stephen ;
Rossmann, Michael G. ;
Rao, Srinivas ;
Nabel, Gary J. .
NATURE MEDICINE, 2010, 16 (03) :334-U134
[4]   Evasion of the Innate Immune Response: the Old World Alphavirus nsP2 Protein Induces Rapid Degradation of Rpb1, a Catalytic Subunit of RNA Polymerase II [J].
Akhrymuk, Ivan ;
Kulemzin, Sergey V. ;
Frolova, Elena I. .
JOURNAL OF VIROLOGY, 2012, 86 (13) :7180-7191
[5]   Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 [J].
Alexopoulou, L ;
Holt, AC ;
Medzhitov, R ;
Flavell, RA .
NATURE, 2001, 413 (6857) :732-738
[6]   Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression [J].
Ali, Mohamed A. E. ;
Fuse, Kyoko ;
Tadokoro, Yuko ;
Hoshii, Takayuki ;
Ueno, Masaya ;
Kobayashi, Masahiko ;
Nomura, Naho ;
Vu, Ha Thi ;
Peng, Hui ;
Hegazy, Ahmed M. ;
Masuko, Masayoshi ;
Sone, Hirohito ;
Arai, Fumio ;
Tajima, Atsushi ;
Hirao, Atsushi .
SCIENTIFIC REPORTS, 2017, 7
[7]   Genetic divergence of Chikungunya viruses in India (1963-2006) with special reference to the 2005-2006 explosive epidemic [J].
Arankalle, Vidya A. ;
Shrivastava, Shubham ;
Cherian, Sarah ;
Gunjikar, Rashmi S. ;
Walimbe, Atul M. ;
Jadhav, Santosh M. ;
Sudeep, A. B. ;
Mishra, Akhilesh C. .
JOURNAL OF GENERAL VIROLOGY, 2007, 88 :1967-1976
[8]   A novel strategy of epitope design in Neisseria gonorrhoeae [J].
Barh, Debmalya ;
Misra, Amarendra Narayan ;
Kumar, Anil ;
Azevedo, Vasco .
BIOINFORMATION, 2010, 5 (02) :77-+
[9]  
Berzofsky J.A., 1993, FUNDAMENTAL IMMUNOL, V5, P631
[10]   Development of an epitope conservancy analysis tool to facilitate the design of epitope-based diagnostics and vaccines [J].
Bui, Huynh-Hoa ;
Sidney, John ;
Li, Wei ;
Fusseder, Nicolas ;
Sette, Alessandro .
BMC BIOINFORMATICS, 2007, 8 (1)