American Journal of Infectious Diseases and Microbiology
ISSN (Print): 2328-4056 ISSN (Online): 2328-4064 Website: http://www.sciepub.com/journal/ajidm Editor-in-chief: Maysaa El Sayed Zaki
Open Access
Journal Browser
Go
American Journal of Infectious Diseases and Microbiology. 2019, 7(1), 26-42
DOI: 10.12691/ajidm-7-1-5
Open AccessArticle

Identification of Novel Multi Epitopes Vaccine against the Capsid Protein (ORF2) of Hepatitis E Virus

Mashair A. A. Nouri1, Yassir A. Almofti1, , Khoubieb Ali Abd-elrahman2 and Elsideeq E. M. Eltilib1

1Department of Molecular Biology and Bioinformatics, College of Veterinary Medicine, University of Bahri, Khartoum- Sudan

2Department of pharmaceutical technology, College of Pharmacy, University of Medical Science and Technology (MUST) Khartoum- Sudan

Pub. Date: October 07, 2019

Cite this paper:
Mashair A. A. Nouri, Yassir A. Almofti, Khoubieb Ali Abd-elrahman and Elsideeq E. M. Eltilib. Identification of Novel Multi Epitopes Vaccine against the Capsid Protein (ORF2) of Hepatitis E Virus. American Journal of Infectious Diseases and Microbiology. 2019; 7(1):26-42. doi: 10.12691/ajidm-7-1-5

Abstract

Hepatitis E virus (HEV) is non-enveloped, small virus with a positive RNA sense in the family Hepeviredae genus Orthohepevirus. More than 20 million individuals annually infected by HEV with increased mortality rate ranged from 8% to 20% in pregnant women. The aim of the present study was to design multi peptides vaccine against HEV using immunoinformatic tools that elicited humoral and cellular immunity. The capsid protein sequences of HEV were retrieved from NCBI and subjected to various immunoinformatics tools from IEDB to assess their conservancy, surface accessibility and antigenicity as promising epitopes against B cells. Moreover the binding affinity of the conserved predicted epitopes was analyzed against MHC-I and MHC-II alleles of the T cells. The predicted epitopes were further assessed for their population coverage. For B-cell 32, 23 and 12 epitopes were predicted as linear conserved epitopes, surface accessibility and antigenic respectively. However the best B cell epitopes that overlapped the prediction tools were 165PLQD168, 219PTSVD223, 452PTPSPAPS459, 556GYPYNY561 and 615DYPA619. For T cell, the MHC-I alleles interacted with 37 conserve epitopes. Four epitopes (367GIALTLFNL375, 379LLGGLPTEL387, 389SSAGGQLFY397 and 394QLFYSRPVV402) interacted with MHC class-I with high affinity and specificity and hence were proposed as vaccine candidates. Moreover seven epitopes out of 125 predicted epitopes (were 205YAISISFWP213, 299LLDFALELE307, 341LTTTAATRF349, 367GIALTLFNL375, 368IALTLFNLA376, 379LLGGLPTEL387 and 394QLFYSRPVV402) were proposed as vaccine since they demonstrated high affinity to MHC-II alleles. The epitopes 367GIALTLFNL375, 379LLGGLPTEL387 and 394QLFYSRPVV402 were recognized interacting with both MHC-I and MHC-II alleles. The population coverage epitopes set for MHC-I and MHC-II alleles was 78.97% and 99.99%, respectively. While the epitopes set for all T cell proposed epitopes was 100%. Thirteen epitopes were predicted eliciting B and T cells and proposed as vaccine candidates against HEV. However these proposed epitopes require clinical trials studies to ensure their efficacy as vaccine candidates.

Keywords:
Hepatitis E Virus capsid protein Immune epitope database (IEDB) epitope B-cell T-cell

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

Figure of 6

References:

[1]  Xiang K, et al., A Recombinant HAV Expressing a Neutralization Epitope of HEV Induces Immune Response against HAV and HEV in Mice. Viruses, 2017. 9(9).
 
[2]  Obana S, et al., Epizootiological study of rodent-borne hepatitis E virus HEV-C1 in small mammals in Hanoi, Vietnam. J Vet Med Sci, 2017. 79(1): p. 76-81.
 
[3]  Baumann-Popczyk A., et al., A cross-sectional study among Polish hunters: seroprevalence of hepatitis E and the analysis of factors contributing to HEV infections. Med Microbiol Immunol, 2017.
 
[4]  Yin X, X Li, and Z. Feng, Role of Envelopment in the HEV Life Cycle. Viruses, 2016. 8(8).
 
[5]  Pan, J.S., et al., Application of truncated immunodominant polypeptide from hepatitis E virus (HEV) ORF2 in an assay to exclude nonspecific binding in detecting anti-HEV immunoglobulin M. J Clin Microbiol, 2010. 48(3): p. 779-84.
 
[6]  Takahashi, M., et al., Prolonged fecal shedding of hepatitis E virus (HEV) during sporadic acute hepatitis E: evaluation of infectivity of HEV in fecal specimens in a cell culture system. J Clin Microbiol, 2007. 45(11): p. 3671-9.
 
[7]  Tang, Z.M., et al., The Bama miniature swine is susceptible to experimental HEV infection. Sci Rep, 2016. 6: p. 31813.
 
[8]  Park, W.-J., et al., Hepatitis E virus as an emerging zoonotic pathogen. Journal of veterinary science, 2016. 17(1): p. 1-11.
 
[9]  Si, F., et al., Construction of an infectious cDNA clone of a swine genotype 3 HEV strain isolated in Shanghai, China. Intervirology, 2014. 57(2): p. 74-82.
 
[10]  Zhu, Y., et al., Determination of the full-genome sequence of hepatitis E virus (HEV) SAAS-FX17 and use as a reference to identify putative HEV genotype 4 virulence determinants. Virol J, 2012. 9: p. 264.
 
[11]  Suneetha, P.V., et al., Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection. Hepatology, 2012. 55(3): p. 695-708.
 
[12]  Wang, M., et al., Acute, Recent and Past HEV Infection among Voluntary Blood Donors in China: A Systematic Review and Meta-Analysis. PLoS One, 2016. 11(9): p. e0161089.
 
[13]  Shimizu, K., et al., Serological evidence of infection with rodent-borne hepatitis E virus HEV-C1 or antigenically related virus in humans. J Vet Med Sci, 2016. 78(11): p. 1677-1681.
 
[14]  Kamar, N., et al., Treatment of HEV Infection in Patients with a Solid-Organ Transplant and Chronic Hepatitis. Viruses, 2016. 8(8).
 
[15]  Candido, A., et al., Diagnosis of HEV infection by serological and real-time PCR assays: a study on acute non-A-C hepatitis collected from 2004 to 2010 in Italy. BMC Res Notes, 2012. 5: p. 297.
 
[16]  Verhoef, L., et al., Seroprevalence of hepatitis E antibodies and risk profile of HEV seropositivity in The Netherlands, 2006-2007. Epidemiol Infect, 2012. 140(10): p. 1838-47.
 
[17]  Takahashi, M., et al., Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) Is highly specific for diagnosis of acute HEV infection. J Clin Microbiol, 2005. 43(1): p. 49-56.
 
[18]  Shrestha, M.P., et al., Safety and efficacy of a recombinant hepatitis E vaccine. New England Journal of Medicine, 2007. 356(9): p. 895-903.
 
[19]  Zhang, J., et al., Long-term efficacy of a hepatitis E vaccine. New England Journal of Medicine, 2015. 372(10): p. 914-922.
 
[20]  Taherkhani, R., M. Makvandi, and F. Farshadpour, Development of enzyme-linked immunosorbent assays using 2 truncated ORF2 proteins for detection of IgG antibodies against hepatitis E virus. Annals of laboratory medicine, 2014. 34(2): p. 118-126.
 
[21]  Bank, B.P.D., National Center of Biotechnology Information (NCBI). National Library of Medicine, NIH, Bethesda, MD, 1994.
 
[22]  Kumar, S., G. Stecher, and K. Tamura, MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Molecular biology and evolution, 2016. 33(7): p. 1870-1874.
 
[23]  Hall, T.A. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. in Nucleic acids symposium series. 1999. [London]: Information Retrieval Ltd., c1979-c2000.
 
[24]  Fleri, W., et al., Immune epitope database and analysis resource. 2016.
 
[25]  Abu-haraz, A.H., et al., Multi Epitope Peptide Vaccine Prediction against Sudan Ebola Virus Using Immuno-Informatics Approaches. Adv Tech Biol Med, 2017. 5(203): p. 2379-1764. 1000203.
 
[26]  Hasan, M.A., M. Hossain, and M.J. Alam, A computational assay to design an epitope-based Peptide vaccine against Saint Louis encephalitis virus. Bioinformatics and Biology insights, 2013. 7: p. 347.
 
[27]  Larsen, J.E., O. Lund, and M. Nielsen, Improved method for predicting linear B-cell epitopes. Immunome research, 2006. 2(1): p. 2.
 
[28]  Emini, E.A., et al., Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. Journal of virology, 1985. 55(3): p. 836-839.
 
[29]  Kolaskar, A. and P.C. Tongaonkar, A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS letters, 1990. 276(1-2): p. 172-174.
 
[30]  Andreatta, M. and M. Nielsen, Gapped sequence alignment using artificial neural networks: application to the MHC class I system. Bioinformatics, 2015. 32(4): p. 511-517.
 
[31]  Lundegaard, C., et al., NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8–11. Nucleic acids research, 2008. 36(suppl_2): p. W509-W512.
 
[32]  Sidney, J., et al., Quantitative peptide binding motifs for 19 human and mouse MHC class I molecules derived using positional scanning combinatorial peptide libraries. Immunome research, 2008. 4(1): p. 2.
 
[33]  Wang, P., et al., Peptide binding predictions for HLA DR, DP and DQ molecules. BMC bioinformatics, 2010. 11(1): p. 568.
 
[34]  Wang, P., et al., A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLoS computational biology, 2008. 4(4): p. e1000048.
 
[35]  Nielsen, M. and O. Lund, NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction. BMC bioinformatics, 2009. 10(1): p. 296.
 
[36]  Nielsen, M., C. Lundegaard, and O. Lund, Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method. BMC bioinformatics, 2007. 8(1): p. 238.
 
[37]  Andreatta, M., et al., Accurate pan-specific prediction of peptide-MHC class II binding affinity with improved binding core identification. Immunogenetics, 2015. 67(11-12): p. 641-650.
 
[38]  Buus, S., et al. Prediction of peptide-MHC class II binding affinity with improved binding core identification; implications for the interpretation of T cell cross-reactivity. in 6th Argentinian Conference on Bioinformatics and Computational Biology. 2015. A2B2C.
 
[39]  Källberg, M., et al., Template-based protein structure modeling using the RaptorX web server. Nature protocols, 2012. 7(8): p. 1511-1522.
 
[40]  Ma, J., et al., Protein threading using context-specific alignment potential. Bioinformatics, 2013. 29(13): p. i257-i265.
 
[41]  Peng, J. and J. Xu, A multiple‐template approach to protein threading. Proteins: Structure, Function, and Bioinformatics, 2011. 79(6): p. 1930-1939.
 
[42]  Bui, H.-H., et al., Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC bioinformatics, 2006. 7(1): p. 153.
 
[43]  Mori, Y. and Y. Matsuura, Structure of hepatitis E viral particle. Virus research, 2011. 161(1): p. 59-64.
 
[44]  Nan, Y., et al., Vaccine development against zoonotic hepatitis E virus: open questions and remaining challenges. Frontiers in Microbiology, 2018. 9: p. 266.
 
[45]  Gu, Y., et al., Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody. Cell research, 2015. 25(5): p. 604.
 
[46]  Tang, Z.-M., et al., A novel linear neutralizing epitope of hepatitis E virus. Vaccine, 2015. 33(30): p. 3504-3511.
 
[47]  Li, S.W., et al., A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine, 2005. 23(22): p. 2893-2901.
 
[48]  Li, S.-W., et al., Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid. Journal of Biological Chemistry, 2005. 280(5): p. 3400-3406.
 
[49]  Behloul, N., et al., Antigenic composition and immunoreactivity differences between HEV recombinant capsid proteins generated from different genotypes. Infection, Genetics and Evolution, 2015. 34: p. 211-220.
 
[50]  Li, T.-C., et al., Expression and self-assembly of empty virus-like particles of hepatitis E virus. Journal of virology, 1997. 71(10): p. 7207-7213.
 
[51]  Li, T.-C., et al., Essential elements of the capsid protein for self-assembly into empty virus-like particles of hepatitis E virus. Journal of virology, 2005. 79(20): p. 12999-13006.
 
[52]  Yamashita, T., et al., Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proceedings of the National Academy of Sciences, 2009. 106(31): p. 12986-12991.
 
[53]  Badawi, M.M., et al., Highly conserved epitopes of Zika envelope glycoprotein may act as a novel peptide vaccine with high coverage: immunoinformatics approach. American Journal of Biomedical Research, 2016. 4(3): p. 46-60.
 
[54]  Perrie, Y., et al., Recent developments in particulate-based vaccines. Recent patents on drug delivery & formulation, 2007. 1(2): p. 117-129.
 
[55]  Bachler, B.C., et al., Novel biopanning strategy to identify epitopes associated with vaccine protection. Journal of virology, 2013. 87(8): p. 4403-4416.