Designing a multi-epitope candidate vaccine against SARS-CoV-2 through in silico approach for producing in plant systems
Multi-epitope vaccine designing for SARS-CoV2
DOI:
https://doi.org/10.24193/subbbiol.2024.1.01Keywords:
COVID-19, SARS-CoV-2, in silico, Multi-epitope candidate vaccine, immunoinformaticsAbstract
The COVID-19 is considered as a type of severe acute respiratory syndrome (SARS-CoV-2). The current pandemic causes a vital destruction in international social and economic systems. Current available vaccines involve entire viruses; however, peptide-based vaccines could be also beneficial. In the present study, a computationally candidate vaccine was designed against SARS-CoV-2. Surface glycoproteins (E, M, and S proteins) and N protein amino acid sequences were analyzed to predict high score of the B and T cell epitopes as antigenic proteins of the virus. High score epitopes, and the B subunit of Vibrio cholerae toxin, as an adjuvant put together by appropriate linkers to construct a multi-epitope candidate vaccine. Bioinformatics tools were used to predict the secondary, tertiary structure and physicochemical properties, such as aliphatic index, theoretical pH, molecular weight, and estimated half-life of the multi-epitope candidate vaccine. The interaction of candidate vaccine with TLR2 and TLR4 was computationally evaluated by molecular docking. Finally, the codon optimization and the secondary structure of mRNA were calculated, and in silico cloning was performed into plant expression vector by SnapGENE. This designed candidate vaccine along with the computational results requires laboratory evaluations to be confirmed as a candidate vaccine against SARS-COV-2 infection.
References
Annunziato, G., & Costantino, G. (2020). Antimicrobial peptides (AMPs): a patent review (2015–2020). Exp Opin Thera Patents, 30(12), 931-947. Doi: 10.1080/13543776.2020.1851679.
Antonio-Herrera, L., Badillo-Godinez, O., Medina-Contreras, O., Tepale-Segura, A., García-Lozano, A., Gutierrez-Xicotencatl, L. Soldevila, G., Esquivel-Guadarrama, F.R., Idoyaga, J. and Bonifaz, L.C. (2018). The nontoxic cholera B subunit is a potent adjuvant for intradermal DC-targeted vaccination. Front Immunol, 9, 2212-2228. Doi: 10.3389/fimmu.2018.02212.
Amanat, F. & Krammer, F. (2020). SARS-CoV-2 vaccines: status report. Immunity, 52(4), 583-589. Doi: 10.1016/j.immuni.2020.03.007.
Apasov, S.G., & Sitkovsky, M.V. (2005). T cell-mediated immunity. In: Principles of Immunopharmacology, Nijkamp FP, Parnham MJ. (ed.), Springer, Singapore, pp. 19-28. Doi: 10.1007/978-3-030-10811-3.
Athari, S.S. (2019). Targeting cell signaling in allergic asthma. Signal Transduct Target Ther, 4(1), 1-19. Doi: 10.1038/s41392-019-0079-0.
Bhat, K.A., Tariq, L., Ayaz, A., Manzoor, M., Zargar, S.M., & Shah, A.A. (2022). Molecular farming: sustainable manufacturing of vaccines, antibodies, and other therapeutic substances. In: Metabolic engineering in plants, Springer Nature, Singapore, pp. 239-261. Doi: 10.1007/978-981-16-7262-0_10.
Boopathi, S., Poma, A.B. & Kolandaivel, P. (2020). Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn, 39(9), 3409-3418. Doi: 10.1080/07391102.2020.1758788.
Braun, J., Loyal, L., Frentsch, M., Wendisch, D., Georg, P., Kurth, F., Hippenstiel, S., Dingeldey, M., Kruse, B., Fauchere, F. & Baysal, E. (2020). SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature, 587(7833), 270-274. Doi: 10.1038/s41586-020-2598-9.
Caparco, A.A., Dautel, D.R., & Champion, J.A. (2022). Protein mediated enzyme immobilization. Small, 18(19), 2106425. Doi: 10.1002/smll.202106425.
Christensen, D. (2016). Vaccine adjuvants: why and how. Hum Vaccines Immunother, 12(10), 2709-2711. Doi: 10.1080%2F21645515.2016.1219003.
Chung, Y.H., Church, D., Koellhoffer, E.C., Osota, E., Shukla, S., Rybicki, E.P., & Steinmetz, N. F. (2022). Integrating plant molecular farming and materials research for next-generation vaccines. Nat Rev Mater, 7(5), 372-388. Doi: 10.1038/s41578-021-00399-5.
Cong, H., Gu, Q.M., Yin, H.E., Wang, J.W., Zhao, Q.L., Zhou, H.Y., Li, Y. & Zhang, J.Q. (2008). Multi-epitope DNA vaccine linked to the A2/B subunit of cholera toxin protect mice against Toxoplasma gondii. Vaccine, 26(31), 3913-3921. Doi: 10.1016/j.vaccine.2008.04.046.
Dibner, J. (2021). Fecal‐oral transmission of COVID‐19: could hypochlorhydria play a role? J Med Virol, 93(1), 166-167. Doi: 10.1002%2Fjmv.26265.
Dong, R., Chu, Z., Yu, F. & Zha, Y. (2020). Contriving multi-epitope subunit of vaccine for COVID-19: immunoinformatics approaches. Front Immunol, 11, 1784-1802. Doi: 10.3389/fimmu.2020.01784.
Dyer, O. (2020). Covid-19: many poor countries will see almost no vaccine next year, aid groups warn. BMJ Br Med J, 371, 1-2. Doi: 10.1136/bmj.m4809.
Eisenbarth, S.C. (2019). Dendritic cell subsets in T cell programming: location dictates function. Nat Rev Immunol, 19(2), 89-103. Doi: 10.1038%2Fs41577-018-0088-1.
Fallahi S, & Mohammadhassan R. (2020). A review of pharmaceutical recombinant proteins and gene transformation approaches in transgenic poultry. J Trop Life Sci, 10(2), 163-173. Doi: 10.11594/jtls.10.02.09.
Fehr, A.R. & Perlman, S. (2015). Coronaviruses, an overview of their replication and pathogenesis, In: Coronaviruses methods in molecular biology, Maier, H., Bickerton, E. & Britton, P. (ed.), Springer, Singapore, pp. 1-23. Doi: 10.1007%2F978-1-4939-2438-7_1.
Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus, J., Dan, J.M., Moderbacher, C.R., Rawlings, S.A., Sutherland, A., Premkumar, L., Jadi, R.S. & Marrama, D. (2020). Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell, 181(7), 1489-1501. Doi: 10.1016/j.cell.2020.05.015.
Hajissa, K., Zakaria, R., Suppian, R. & Mohamed, Z. (2019). Epitope-based vaccine as a universal vaccination strategy against Toxoplasma gonidii infection: a mini-review. J Adv Vet Anim Res, 6(2), 174–182. Doi: 10.5455%2Fjavar.2019.f329.
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X. & Cheng, Z. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506. Doi: 10.1016/S0140-6736(20)30183-5.
Kakkanas, A., Karamichali, E., Koufogeorgou, E.I., Kotsakis, S.D., Georgopoulou, U., & Foka, P. (2022). Targeting the YXXΦ motifs of the SARS coronaviruses 1 and 2 ORF3a peptides by in silico analysis to predict novel virus—host interactions. Biomolecules, 12(8), 1052. Doi: 10.3390/biom12081052.
Kar, T., Narsaria, U., Basak, S., Deb, D., Castiglione, F., Mueller, D.M. & Srivastava, A.P. (2020). A candidate multi-epitope vaccine against SARS-CoV-2. Sci Rep, 10(1), 1-24. Doi: 10.1038/s41598-020-67749-1.
Kaur, R., Arora, N., Jamakhani, M.A., Malik, S., Kumar, P., Anjum, F., Tripathi, S., Mishra, A. & Prasad, A. (2020). Development of multi-epitope chimeric vaccine against Taenia solium by exploring its proteome: an in silico approach. Expert Rev Vaccines, 19(1), 105-114. Doi: 10.1080/14760584.2019.1711057.
Khan, S., Shafiei, M. S., Longoria, C., Schoggins, J. W., Savani, R. C., & Zaki, H. (2021). SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway. Elife, 10, e68563. Doi: 10.7554/eLife.68563.
Le, T.T., Andreadakis, Z., Kumar, A., Román, R.G., Tollefsen, S., Saville, M., & Mayhew, S. (2020). The COVID-19 vaccine development landscape. Nat Rev Drug Discov, 19(5), 305-306. Doi: 10.1038/d41573-020-00073-5.
Lichtenstein, B. R., & Höcker, B. (2018). Engineering an AB5 protein carrier. Sci Rep, 8(1), 1-11. Doi: 10.1038/s41598-018-30910-y.
Lim, Y.X., Ng, Y.L., Tam, J.P. & Liu, D.X. (2016). Human coronaviruses: a review of virus–host interactions. Diseases, 4(3), 26-54. Doi: 10.3390/diseases4030026.
Liu, Z. & Chen, Y.H. (2004). Design and construction of a recombinant epitope-peptide gene as a universal epitope-vaccine strategy. J Immunol Methods, 285(1), 93-97. Doi: 10.1016/j.jim.2003.10.018.
Margolin, E., Crispin, M., Meyers, A., Chapman, R., & Rybicki, E.P. (2020a). A roadmap for the molecular farming of viral glycoprotein vaccines: engineering glycosylation and glycosylation-directed folding. Front Plant Sci, 11, 609207. Doi: 10.3389/fpls.2020.609207.
Margolin, E., Verbeek, M., Meyers, A., Chapman, R., Williamson, A.L., & Rybicki, E.P. (2020b). Calreticulin co-expression supports high level production of a recombinant SARS-CoV-2 spike mimetic in Nicotiana benthamiana. BioRxiv, 2020-06. Doi: 10.1101/2020.06.14.150458.
María, R.R., Arturo, C.J., Alicia, J.A., Paulina, M.G. & Gerardo, A.O. (2017). The impact of bioinformatics on vaccine design and development, In: Vaccines, Afrin, F., Hemeg, H. & Ozbak, H. (eds.), IntechOpen, London, pp. 3-6. Doi: 10.5772/intechopen.69273.
Miles, S., Portela, M., Cyrklaff, M., Ancarola, M.E., Frischknecht, F., Durán, R., Dematteis, S. & Mourglia‐Ettlin, G. (2019). Combining proteomics and bioinformatics to explore novel tegumental antigens as vaccine candidates against Echinococcus granulosus infection. J Cell Biochem, 120(9), 15320-36. Doi: 10.1002/jcb.28799.
Mohammadhassan, R., & Asadishad, T. (2023). Using in silico tools to analyze the 5ʹ untranslated regions of the alcohol dehydrogenase gene from Arabidopsis thaliana and Omega Sequence. Makara J Sci, 27(4), 8. Doi: 10.7454/mss.v27i4.1472.
Mohammadhassan, R., Fallahi, S. & Mohammadalipour, Z. (2020). ADMET and pharmaceutical activity analysis of caffeic acid diversities by in silico tools. Lett Appl NanoBioSci, 9(1), 840-8. Doi: 10.33263/LIANBS91.840848.
Mohammadhassan, R., Esfahani, K. & Kashefi, B. (2018). Constructional and functional evaluation of two new plant expression vectors—pBI121 gus-6 and pBI121 5+1. Banat J Biotechnol, 9(17), 60-68. Doi: 10.7904/2068–4738–IX(17)–60.
Mohammadhassan. R., Kashefi, B. & Delcheh, K.S. (2014). Agrobacterium-based vectors: a review. Int J Farm All Sci, 3(9), 1002-1008. http://ijfas.com/wp-content/uploads/2014/10/1002-1008.pdf.
Nokhostin, F., Dargahi MalAmir, M., Tutunchi, S., & Rezaeeyan, H. (2020). Evaluation of prognostic/diagnostic value of Hematological markers in the detection of inflammation in coronavirus disease: a review study. JAdv Med Biomed Res, 28(128), 171-174. Doi: 10.30699/jambs.28.128.171.
Peters, B., Nielsen, M., & Sette, A. (2020). T cell epitope predictions. Annu Rev Immunol, 38, 123-145. Doi: 10.1146/annurev-immunol-082119-124838.
Rahbaran, M., Razeghian, E., Maashi, M.S., Jalil, A.T., Widjaja, G., Thangavelu, L., & Jarahian, M. (2021). Cloning and embryo splitting in mammalians: brief history, methods, and achievements. Stem Cells Int, 2021, 1-11. Doi: 10.1155/2021/2347506.
Rahbaran, M. (2021). Pregnancy and Covid-19: a brief review. 1st National Conference in Health, Social sciences and Humanities focusing on COVID19. Tbilisi, Georgia. https://b2n.ir/360005637.
Ratre, Y.K., Mehta, A., Shinde, S., Sinha, V., Soni, V.K., Sonkar, S.C., & Vishvakarma, N.K. (2023). Molecular farming and anticancer vaccine: current opportunities and openings. In: Microbial bioreactors for industrial molecules, Singh S.P. & Upadhyay, S.K. (eds), Wiley, Hoboken, pp. 355-373. Doi: 10.1002/9781119874096.ch17.
Reynisson, B., Alvarez, B., Paul, S., Peters, B., & Nielsen, M. (2020). NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nuc Acids Res, 48(W1), W449-W454. Doi: 10.1093%2Fnar%2Fgkaa379.
Shah, V.K., Firmal, P., Alam, A., Ganguly, D. & Chattopadhyay, S. (2020). Overview of immune response during SARS-CoV-2 infection: lessons from the past. Front Immunol, 11, 1949-66. Doi: 10.3389/fimmu.2020.01949.
Shrotri, M., van Schalkwyk, M.C., Post, N., Eddy, D., Huntley, C., Leeman, D., Rigby, S., Williams, S.V., Bermingham, W.H., Kellam, P. & Maher, J. (2021). T cell response to SARS-CoV-2 infection in humans: a systematic review. PloS one, 16(1), e0245532. Doi: 10.1371/journal.pone.0245532.
Sheik Amamuddy, O., Veldman, W., Manyumwa, C., Khairallah, A., Agajanian, S., Oluyemi, O., Verkhivker, G.M. & Tastan Bishop, Ö. (2020). Integrated computational approaches and tools for allosteric drug discovery. Int J Mol Sci, 21(3), 847. Doi: 10.3390/ijms21030847.
Shey, R.A., Ghogomu, S.M., Esoh, K.K., Nebangwa, N.D., Shintouo, C.M., Nongley, N.F., Asa, B.F., Ngale, F.N., Vanhamme, L. & Souopgui, J. (2019). In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases. Sci Rep, 9(1), 4409. Doi: 10.1038/s41598-019-40833-x.
Siebenmorgen, T., & Zacharias, M. (2020). Computational prediction of protein–protein binding affinities. Wiley Interdiscip Rev: Computat Mol Sci, 10(3), e1448.
Smith, K.G., Kamdar, A.A. & Stark, J.M. (2019). Lung defenses: intrinsic, innate, and adaptive. In: Kendig’s disorders of the respiratory tract in children, Wilmott, R.W., Li, A., Sly, P., Bush, A., Deterding, R. & Ratjen, F. (eds.), Elsevier, Amsterdam, pp. 120-133. Doi: 10.1016/C2015-0-01292-8.
Suárez-Fueyo, A., Crispín, J.C. & Tsokos, G.C. (2019). T cells. In: Dubois’ lupus erythematosus and related syndromes, Wallace, D.J. & Hahn, B.H. (eds.), Elsevier, Amsterdam, pp. 116-124. Doi: 10.1016/C2010-0-66018-4.
van der Donk, L.E., Eder, J., van Hamme, J.L., Brouwer, P.J., Brinkkemper, M., van Nuenen, A.C., van Gils, M.J., Sanders, R.W., Kootstra, N.A., Bermejo‐Jambrina, M. & Geijtenbeek, T.B. (2022). SARS‐CoV‐2 infection activates dendritic cells via cytosolic receptors rather than extracellular TLRs. European J Immunol, 52(4), 646-655. Doi: 10.1002/eji.202149656.
van Elslande, J., Decru, B., Jonckheere, S., van Wijngaerden, E., Houben, E., Vandecandelaere, P., Indevuyst, C., Depypere, M., Desmet, S., André, E. & van Ranst, M. (2020). Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs. Clin Microbiol Infect, 26(11), e1-7. Doi: 10.1016/j.cmi.2020.07.038.
Walker, J.M. (2005). The proteomics protocols handbook, Springer, New York. Doi: 10.1385/1592598900.
Wiedinger, K., Pinho, D. & Bitsaktsis, C. (2017). Utilization of cholera toxin B as a mucosal adjuvant elicits antibody-mediated protection against S. pneumoniae infection in mice. Ther Adv Vaccines, 5(1), 15-24. Doi: 10.1177/2051013617691041.
Yang, J. & Zhang, Y. (2015). I-TASSER server: new development for protein structure and function predictions. Nucleic Acids Res, 43(W1), W174-81. Doi: 10.1093/nar/gkv342.
Yao, Y., Subedi, K., Liu, T., Khalasawi, N., Pretto-Kernahan, C.D., Wotring, J.W., Wang, J., Yin, C., Jiang, A., Fu, C. & Dimitrion, P. (2022). Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes. Cell Discov, 8(1), 89. Doi: 10.1038/s41421-022-00453-8.
Yoshimoto, FK. (2020). The proteins of severe acute respiratory syndrome coronavirus-2 (SARS CoV-2 or n-COV19), the cause of COVID-19. Protein J, 39(3), 198-216. Doi: 10.1007/s10930-020-09901-4.
Zaheer, T., Waseem, M., Waqar, W., Dar, H.A., Shehroz, M., Naz, K., Ishaq, Z., Ahmad, T., Ullah, N., Bakhtiar, S.M. & Muhammad, S.A. (2020). Anti-COVID-19 multi-epitope vaccine designs employing global viral genome sequences. Peer J, 8, e9541. Doi: 10.7717/peerj.9541.
Zheng, C., Shao, W., Chen, X., Zhang, B., Wang, G., & Zhang, W. (2022). Real-world effectiveness of COVID-19 vaccines: a literature review and meta-analysis. Int J Infect Dis, 114, 252-260. Doi: 10.1016/j.ijid.2021.11.009.
Zheng, M., Karki, R., Williams, E.P., Yang, D., Fitzpatrick, E., Vogel, P., Jonsson, C.B. & Kanneganti, T.D. (2021). TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol, 22(7), 829-838. Doi: 10.1038/s41590-021-00937-x.
Zhou, P., Yang, X.L., Wang, X.G., Hu, B., Zhang, L., Zhang, W., Si, H.R., Zhu, Y., Li, B., Huang, C.L. & Chen, H.D. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270-273. Doi: 10.1038/s41586-020-2012-7.
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