Modeling and in Silico Analysis for Prediction of Epitopes Vaccine against Norwalk virus from Capsid Protein (VP1) through Reverse Vaccinology

Elsideeq E. M. Eltilib¹, Yassir A. Almofti^1, , Khoubieb Ali Abd-elrahman² and Mashair A. A. Nouri¹

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

Cite this paper:
Elsideeq E. M. Eltilib, Yassir A. Almofti, Khoubieb Ali Abd-elrahman and Mashair A. A. Nouri. Modeling and in Silico Analysis for Prediction of Epitopes Vaccine against Norwalk virus from Capsid Protein (VP1) through Reverse Vaccinology. American Journal of Infectious Diseases and Microbiology. 2020; 8(1):29-44. doi: 10.12691/ajidm-8-1-5

Abstract

Noroviruses are the leading cause of acute gastroenteritis and is responsible for approximately 685 million cases and 200,000 deaths annually worldwide. Currently, there is no vaccine to prevent human norovirus infection, and there is no specific therapy available to treat it. This study aimed to predict epitopes from the capsid VP1 protein that elicited the immune system and acted as safer efficacious vaccine. A total of 21 noroviurse strains were retrieved from the NCBI database. The IEDB analysis resources were used for epitopes prediction against B and T cells. The population coverage was calculated for the proposed epitopes against the whole world. Eight epitopes (₄₈QVNP₅₁, ₁₅₉EVPLE₁₆₃, ₂₂₄VEQK₂₂₇, ₂₄₅RAPLP₂₄₉, ₃₇₆ISPPS₃₈₀, ₄₀₉VYPP₄₁₂, ₄₇₃FKAY₄₇₆ and ₄₉₂PQQLP₄₉₆) successfully passed all B cell prediction tools and were shown to be antigenic, nonallergic and nontoxic. Thus were proposed as B cells epitopes. For cytotoxic T cells, a total of 103 epitopes were found to interact with MHC-I alleles. However, only 22 epitopes were shown to be antigenic, nonallergic and nontoxic. Among them four epitopes namely (_140-AQATLFPHV-₁₄₈; _216-FLFLVPPTV_-224; _499-GVFVFVSWV_-507 and _410-YPPGFGEVL_-418) interacted with high number of MHC-I alleles and demonstrated favourable population coverage and thus were proposed as cytotoxic T lymphocytes MHC-1 epitopes. Moreover helper T cells, a total of 421 core epitopes were found to interact with MHC-П alleles. However, only 105 epitopes were shown to be antigenic, nonallergic and nontoxic. Eight epitopes namely (_216-FLFLVPPTV_-224; _499-GVFVFVSWV_-507; _433-LPCLLPQEY_-441; _90-NPFLLHLSQ_-98; _394-NYGSSITEA_-402; _247-PLPISSMGI_-255; _220-VPPTVEQKT_-228; _410-YPPGFGEVL_-418) were interacted with most frequent MHC class II alleles, demonstrated higher population coverage and three of them (_216-FLFLVPPTV-224; _499-GVFVFVSWV_-507 and _410-YPPGFGEVL_-418) were shown to interact with both MHC-I and MHC-II alleles. Therefore they were proposed as T helper cells epitopes. The population coverage was 60.35% and 99.96% for MHC-I and MHC-II epitopes, respectively, and 100% for all T cells epitopes. Taken together 17 epitopes successfully proposed as vaccine candidate against noroviruse. In vivo and in vitro clinical trials studies are required to elucidate the effectiveness of these epitopes as vaccine.

Keywords:
Noroviruses NCBI IEDB Insilico vaccine B cells T cells

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References:

[1]	Lopman, B. Global Burden of Norovirus and Prospects for Vaccine Development. CDC Foundation. Available online: https: //www.cdc.gov/norovirus/downloads/global-burden-report.pdf. 2015 (accessed on9 September 2017).
[2]	Centers for Disease Control and Prevention. Norovirus Worldwide. 2016. Available online: https: //www.cdc.gov/norovirus/worldwide.html (accessed on 9 September 2017).
[3]	Ahmed, S.M.; Hall, A.J.; Robinson, A.E.; Verhoef, L.; Premkumar, P.; Parashar, U.D.; Koopmans, M.; Lopman, B.A. Global prevalence of norovirus in cases of gastroenteritis: A systematic review and meta-analysis. Lancet Infect. Dis. 2014, 14, 725-730.
[4]	Bartsch, S.M.; Lopman, B.A.; Ozawa, S.; Hall, A.J.; Lee, B.Y. Global economic burden of norovirus gastroenteritis. PLoS ONE 2016, 11, e0151219.
[5]	Chan, M.C.; Sung, J.J.; Lam, R.K.; Chan, P.K.; Lee, N.L.; Lai, R.W.; Leung, W.K. Fecal viral load and norovirus-associated gastroenteritis. Emerg. Infect. Dis. 2006, 12, 1278-1280.
[6]	Teunis, P.F.M.; Moe, C.L.; Liu, P.; Miller, S.E.; Lindesmith, L.; Baric, R.S.; Le Pendu, J.; Calderon, R.L. Norwalk virus: How infectious is it? J. Med. Virol. 2008, 80, 1468-1476.
[7]	Karst, S.M.; Wobus, C.E.; Lay, M.; Davidson, J.; Virgin, H.W. STAT1-dependent innate immunity to a Norwalk-like virus. Science 2003, 299, 1575-1578.
[8]	Velasquez LS, Hjelm BE, Arntzen CJ, Herbst-Kralovetz MM. An intranasally delivered Toll-like receptor 7 agonist elicits robust systemic and mucosal responses to Norwalk virus-like particles. Clinical and vaccine immunology: CVI. 2010; 17(12): 1850-8.
[9]	Ramani S, Neill FH, Opekun AR, Gilger MA, Graham DY, Estes MK, et al. Mucosal and Cellular Immune Responses to Norwalk Virus. The Journal of infectious diseases. 2015; 212(3): 397-405.
[10]	Kavanagh O, Estes MK, Reeck A, Raju RM, Opekun AR, Gilger MA, et al. Serological responses to experimental Norwalk virus infection measured using a quantitative duplex time-resolved fluorescence immunoassay. Clinical and vaccine immunology : CVI. 2011; 18(7): 1187-90.
[11]	Czako R, Atmar RL, Opekun AR, Gilger MA, Graham DY, Estes MK. Serum hemagglutination inhibition activity correlates with protection from gastroenteritis in persons infected with Norwalk virus. Clinical and vaccine immunology : CVI. 2012; 19(2): 284-7.
[12]	Vongpunsawad S, Venkataram Prasad BV, Estes MK. Norwalk Virus Minor Capsid Protein VP2 Associates within the VP1 Shell Domain. Journal of virology. 2013; 87(9): 4818-25.
[13]	Liu P, Yuen Y, Hsiao HM, Jaykus LA, Moe C. Effectiveness of liquid soap and hand sanitizer against Norwalk virus on contaminated hands. Applied and environmental microbiology. 2010; 76(2): 394-9.
[14]	McCarthy M, Estes MK, Hyams KC. Norwalk-like virus infection in military forces: epidemic potential, sporadic disease, and the future direction of prevention and control efforts. The Journal of infectious diseases. 2000; 181 Suppl 2: S387-91.
[15]	Tamura M, Natori K, Kobayashi M, Miyamura T, Takeda N. Interaction of recombinant norwalk virus particles with the 105-kilodalton cellular binding protein, a candidate receptor molecule for virus attachment. Journal of virology. 2000; 74(24): 11589-97.
[16]	Kobayashi S, Sakae K, Suzuki Y, Shinozaki K, Okada M, Ishiko H, et al. Molecular cloning, expression, and antigenicity of Seto virus belonging to genogroup I Norwalk-like viruses. Journal of clinical microbiology. 2000; 38(9): 3492-4.
[17]	Sharp TM, Crawford SE, Ajami NJ, Neill FH, Atmar RL, Katayama K, et al. Secretory pathway antagonism by calicivirus homologues of Norwalk virus nonstructural protein p22 is restricted to noroviruses. Virology journal. 2012; 9: 181.
[18]	Shoemaker GK, van Duijn E, Crawford SE, Uetrecht C, Baclayon M, Roos WH, et al. Norwalk virus assembly and stability monitored by mass spectrometry. Molecular & cellular proteomics : MCP. 2010; 9(8): 1742-51.
[19]	Czako R, Atmar RL, Opekun AR, Gilger MA, Graham DY, Estes MK. Experimental human infection with Norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity. Clinical and vaccine immunology: CVI. 2015; 22(2): 221-8.
[20]	Chen Z, Sosnovtsev SV, Bok K, Parra GI, Makiya M, Agulto L, et al. Development of Norwalk virus-specific monoclonal antibodies with therapeutic potential for the treatment of Norwalk virus gastroenteritis. Journal of virology. 2013; 87(17): 9547-57.
[21]	Atmar RL, Bernstein DI, Harro CD, Al-Ibrahim MS, Chen WH, Ferreira J, et al. Norovirus vaccine against experimental human Norwalk Virus illness. The New England journal of medicine. 2011; 365(23): 2178-87.
[22]	Lindesmith LC, Donaldson E, Leon J, Moe CL, Frelinger JA, Johnston RE, et al. Heterotypic humoral and cellular immune responses following Norwalk virus infection. Journal of virology. 2010; 84(4): 1800-15.
[23]	Ball JM, Hardy ME, Atmar RL, Conner ME, Estes MK. Oral immunization with recombinant Norwalk virus-like particles induces a systemic and mucosal immune response in mice. Journal of virology. 1998; 72(2): 1345-53.
[24]	Asanaka M, Atmar RL, Ruvolo V, Crawford SE, Neill FH, Estes MK. Replication and packaging of Norwalk virus RNA in cultured mammalian cells. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102(29): 10327-32.
[25]	Nakata S, Honma S, Numata KK, Kogawa K, Ukae S, Morita Y, et al. Members of the family caliciviridae (Norwalk virus and Sapporo virus) are the most prevalent cause of gastroenteritis outbreaks among infants in Japan. The Journal of infectious diseases. 2000; 181(6): 2029-32.
[26]	Qu L, Vongpunsawad S, Atmar RL, Prasad BV, Estes MK. Development of a Gaussia luciferase-based human norovirus protease reporter system: cell type-specific profile of Norwalk virus protease precursors and evaluation of inhibitors. Journal of virology. 2014; 88(18): 10312-26.
[27]	Ajami NJ, Barry MA, Carrillo B, Muhaxhiri Z, Neill FH, Prasad BV, et al. Antibody responses to norovirus genogroup GI.1 and GII.4 proteases in volunteers administered Norwalk virus. Clinical and vaccine immunology : CVI. 2012; 19(12): 1980-3.
[28]	Thorne LG, Goodfellow IG. Norovirus gene expression and replication. J Gen Virol. 2014; 95: 278-291.
[29]	Claire P. Mattison, Cristina V. Cardemil & Aron J. Hall: Progress on Norovirus vaccine research: Public health considerations and future directions, Expert Review of Vaccines.
[30]	Tacket CO, Mason HS, Losonsky G, Estes MK, Levine MM, Arntzen CJ. Human immune responses to a novel norwalk virus vaccine delivered in transgenic potatoes. The Journal of infectious diseases. 2000; 182(1): 302-5.
[31]	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.
[32]	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.
[33]	Jespersen, M.C., Peters, B., Nielsen, M., Marcatili, P. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res. 2017; 45, W24-W29.
[34]	Emini, E.A., Hughes, J.V., Perlow, D., Boger, J. Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide. J. Virol. 1985; 55, 836-839.
[35]	Kolaskar, A., Tongaonkar, P.C. A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett. 1990; 276, 172-174.
[36]	Dimitrov, I., Naneva, L., Doytchinova, I.A., Bangov, I. Allergen FP: allergenicity prediction by descriptor fingerprints. Bioinformatics. 2014; 30, 846-851.)
[37]	Dimitrov et al., 2013 Dimitrov, I., Bangov, I., Flower, D.R., Doytchinova, I.A. AllerTOP v.2- a server for in silico prediction of allergens. J Mol. Model. 2013; 20, 2278.
[38]	Fiers, M.W.E.J., Kleter, G.A., Nijland, H., Peijnenburg, A., Nap, J.P., Ham, R. Allermatch™, a webtool for the prediction of potential allergenicity according to current FAO/WHO Codex alimentarius guidelines. BMC Bioinform. 2004; 5, 133.
[39]	Chrysostomou, C., Seker, H. Prediction of protein allergenicity based on signal-processing bioinformatics approach. In: 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. 2014.
[40]	Gupta, S., Kapoor, P., Chaudhary, K., Gautam, A., Kumar, R. Open source drug discovery consortium, Raghava GP in silico approach for predicting toxicity of pep-tides and proteins. PLoS One. 2013; 8 (9), e73957.
[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]	Glass RI, Parashar UD, Estes MK. Norovirus gastroenteritis. N Engl J Med. 2009; 361: 1776-85.
[43]	Ettayebi K, Crawford SE, Murakami K, et al. Replication of human noroviruses in stem cell-derived human enteroids. Science. 2016; 353(6306): 1387-1393
[44]	Tucker SN, Tingley DW, Scallan CD. Oral adenoviral-based vaccines: historical perspective and future opportunity. Exp Rev Vaccines. 2008; 7: 25-31.
[45]	Guo L, Wang J, Zhou H, et al. Intranasal administration of a recombinant adenovirus expressing the norovirus capsid protein stimulates specific humoral, mucosal, and cellular immune responses in mice. Vaccine. 2008; 26; 460-468.
[46]	Guo L, Zhou H, Wang M, et al. A recombinant adenovirus prime-virus-like particle boost regimen elicits effective and specific immunities against norovirus in mice. Vaccine. 2009; 27: 5233-5238.
[47]	Azim KF, Mahmudul H, Hossain Md N, Somana SR et al. Immunoinformatics approaches for designing a novel multi epitope peptide vaccine against human norovirus (Norwalk virus). Infection, Genetics and Evolution. 2019; 74 (103936)
[48]	Black M, Trent A, Tirrell M, Olive C. Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert review of vaccines. 2010; 9(2): 157-73.
[49]	Hasan, M., Azim, K.F., Begum, A., Khan, N.A., Shammi, T.S., Imran, A.S., Chowdhury, I.M., Urme, S.R. Vaccinomics strategy for developing a unique multi-epitope monovalent vaccine against Marburg marburgvirus. Infect. Genet. Evol. 2019; 70, 140-157.
[50]	Garcia, K.C., Teyton, L., Wilson, I.A. Structural basis of T cell recognition. Annu. Rev. Immunol. 1999; 17, 369-397.
[51]	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.