Computational Approaches To Design Multi Epitope-Based Vaccine Designing of Dengue virus -2 Enveloped Protein For Dengue Virus: Multi Epitope-Based Vaccine Designing of Dengue Virus

Hamna Tariq; Mehvish Mumtaz; Tuba Aslam; Hafiz Muhammad Husnain Azam; Nazim Hussain; Muhammad Ali; Hadia Sarfraz; Moeen Zulfiqar; Zulqarnain Baqar; Haris Munir

doi:10.54393/pjhs.v5i03.1341

Authors

Hamna Tariq Department of Molecular Biology, University of Okara, Renala Khurd, Pakistan
Mehvish Mumtaz Department of Molecular Biology, University of Okara, Renala Khurd, Pakistan
Tuba Aslam Department of Molecular Biology, University of Okara, Renala Khurd, Pakistan
Hafiz Muhammad Husnain Azam Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Universitätsplatz 1, 01968, Senftenberg, Germany
Nazim Hussain Centre For Applied Molecular Biology (CAMB), University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan
Muhammad Ali Centre for Applied Molecular Biology (CAMB), University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan
Hadia Sarfraz Department of Molecular Biology, University of Okara, Renala Khurd, Pakistan
Moeen Zulfiqar Department of Molecular Biology, University of Okara, Renala Khurd, Pakistan
Zulqarnain Baqar Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong, China
Haris Munir Department of Molecular Biology, University of Okara, Renala Khurd, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v5i03.1341

Keywords:

In silico approach, Vaccine, Dengue Virus, Enveloped Protein

Abstract

Dengue Fever (DF) is a viral disease transmitted by mosquitoes and is a global concern. A successful vaccine for dengue should induce both neutralizing antibodies and cell-mediated immunity. However, no vaccine currently exists for DF. A multi-epitope vaccine offers a promising strategy for preventing such infections. Objective: To create a dengue virus-2 strain multi-epitope vaccine that is safe, non-allergic, and stimulates a strong immune response. Methods: Leveraging in silico tools, we retrieved and analyzed Dengue virus-2 protein sequences, determining antigenicity using VaxiJen version 2.0 and assessing allergenicity using AllerTop. T-cell epitopes were identified via Immune Epitope Database (IEBD) server for Major Histocompatibility Complex -I (MHC-I) and Major Histocompatibility Complex -II (MHC-II) binding and B-cell epitopes were anticipated through IEBD Linear Epitope Prediction Tool v2.0. Analysis of population coverage estimated the prevalence of MHC alleles interacting with the identified epitopes. A multi-epitope vaccine construct integrated adjuvants, universal linkers, and epitopes, evaluated for physicochemical properties, toxicity, secondary, and tertiary structures. Results: Antigenicity analysis identified highly antigenic Dengue virus-2 protein sequences with low allergenicity. T-cell epitopes revealed multiple epitopes with diverse MHC-I and MHC-II affinity, encompassing conserved regions for potential universal vaccine development. Nine non-toxic, non-allergenic B-cell epitopes were identified. Population coverage analysis demonstrated over 71% prevalence of MHCs binding to identified epitopes across diverse populations. Physicochemical assessments revealed favorable characteristics, including immunogenicity and stability. Tertiary structure prediction illustrated the vaccine's 3D arrangement, validated through Ramachandran plots, exhibiting high-quality protein structure. Conclusions: This multieiptope based vaccine is more immunogenic but further in-vitro and in-vivo study is required for its clinical use

References

Azeeze MS and Arivuselvam R. Immuno-informatics design of a multimeric epitope peptide-based vaccine against dengue virus serotype-2. Vacunas. 2023 Oct; 24(4): 380-93. doi: 10.1016/j.vacun.2023.04.001. DOI: https://doi.org/10.1016/j.vacun.2023.04.001

Wong LP and AbuBakar S. Health beliefs and practices related to dengue fever: a focus group study. PLoS neglected tropical diseases. 2013 Jul; 7(7): e2310. doi: 10.1371/journal.pntd.0002310. DOI: https://doi.org/10.1371/journal.pntd.0002310

Tsheten T, Gray DJ, Clements AC, Wangdi K. Epidemiology and challenges of dengue surveillance in the WHO South-East Asia Region. Transactions of The Royal Society of Tropical Medicine and Hygiene. 2021 Jun; 115(6): 583-99. doi: 10.1093/trstmh/traa158. DOI: https://doi.org/10.1093/trstmh/traa158

Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL et al. The global distribution and burden of dengue. Nature. 2013 Apr; 496(7446): 504-7. doi: 10.1038/nature12060. DOI: https://doi.org/10.1038/nature12060

Brady OJ and Hay SI. The global expansion of dengue: how Aedes aegypti mosquitoes enabled the first pandemic arbovirus. Annual Review of Entomology. 2020 Jan; 65: 191-208. doi: 10.1146/annurev-ento-011019-02491. DOI: https://doi.org/10.1146/annurev-ento-011019-024918

Basu P and Bhattacharya S. A new dimension in the dengue epidemiology with special reference to the genetic diversity of the virus: a review. International Journal of Fauna and Biological Studies. 2016; 3: 29-41.

Norazharuddin H and Lai NS. Roles and prospects of dengue virus non-structural proteins as antiviral targets: an easy digest. The Malaysian Journal of Medical Sciences: MJMS. 2018 Sep; 25(5): 6. doi: 10.21315/mjms2018.25.5.2. DOI: https://doi.org/10.21315/mjms2018.25.5.2

Yu IM, Holdaway HA, Chipman PR, Kuhn RJ, Rossmann MG, Chen J. Association of the pr peptides with dengue virus at acidic pH blocks membrane fusion. Journal of Virology. 2009 Dec; 83(23): 12101-7. doi: 10.1128/JVI.01637-09. DOI: https://doi.org/10.1128/JVI.01637-09

Prompetchara E, Ketloy C, Thomas SJ, Ruxrungtham K. Dengue vaccine: Global development update. Asian Asian Pacific Journal of Allergy and Immunology. 2020 Sep; 38(3): 178-85.

Ali M, Pandey RK, Khatoon N, Narula A, Mishra A, Prajapati VK. Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection. Scientific Reports. 2017 Aug; 7(1): 9232. doi: 10.1038/s41598-017-09199-w. DOI: https://doi.org/10.1038/s41598-017-09199-w

Kuo L, Hurst-Hess KR, Koetzner CA, Masters PS. Analyses of coronavirus assembly interactions with interspecies membrane and nucleocapsid protein chimeras. Journal of Virology. 2016 May; 90(9): 4357-68. doi: 10.1128/JVI.03212-15. DOI: https://doi.org/10.1128/JVI.03212-15

Reginald K, Chan Y, Plebanski M, Poh CL. Development of peptide vaccines in dengue. Current Pharmaceutical Design. 2018 Mar; 24(11): 1157-73. doi: 10.2174/1381612823666170913163904. DOI: https://doi.org/10.2174/1381612823666170913163904

Islam R, Parvez MS, Anwar S, Hosen MJ. Delineating blueprint of an epitope-based peptide vaccine against the multiple serovars of dengue virus: A hierarchical reverse vaccinology approach. Informatics in Medicine Unlocked. 2020 Jan; 20: 100430. doi: 10.1016/j.imu.2020.100430. DOI: https://doi.org/10.1016/j.imu.2020.100430

D’Angelo SP, Larkin J, Sosman JA, Lebbé C, Brady B, Neyns B et al. Efficacy and safety of nivolumab alone or in combination with ipilimumab in patients with mucosal melanoma: a pooled analysis. Journal of Clinical Oncology. 2017 Jan; 35(2): 226. doi: 10.1200/JCO.2016.67.9258. DOI: https://doi.org/10.1200/JCO.2016.67.9258

Dhanda SK, Mahajan S, Paul S, Yan Z, Kim H, Jespersen MC et al. IEDB-AR: immune epitope database—analysis resource in 2019. Nucleic Acids Research. 2019 Jul; 47(W1): W502-6. doi: 10.1093/nar/gkz452. DOI: https://doi.org/10.1093/nar/gkz452

Esmailnia E, Amani J, Gargari SL. Identification of novel vaccine candidate against Salmonella enterica serovar Typhi by reverse vaccinology method and evaluation of its immunization. Genomics. 2020 Sep; 112(5): 3374-81. doi: 10.1016/j.ygeno.2020.06.022. DOI: https://doi.org/10.1016/j.ygeno.2020.06.022

Iwasaki A and Yang Y. The potential danger of suboptimal antibody responses in COVID-19. Nature Reviews Immunology. 2020 Jun; 20(6): 339-41. doi: 10.1038/s41577-020-0321-6. DOI: https://doi.org/10.1038/s41577-020-0321-6

Gupta S, Kapoor P, Chaudhary K, Gautam A, Kumar R, Raghava GP. Peptide toxicity prediction. Computational peptidology. 2015: 143-57. doi: 10.1007/978-1-4939-2285-7_7. DOI: https://doi.org/10.1007/978-1-4939-2285-7_7

Pandey RK, Bhatt TK, Prajapati VK. Novel immunoinformatics approaches to design multi-epitope subunit vaccine for malaria by investigating anopheles salivary protein. Scientific reports. 2018 Jan; 8(1): 1125. doi: 10.1038/s41598-018-19456-1. DOI: https://doi.org/10.1038/s41598-018-19456-1

Lindsey NP, Lehman JA, Staples JE, Fischer M. Division of Vector-Borne Diseases. National Center for Emerging and Zoonotic Infectious Diseases, CDC. West Nile virus and other arboviral diseases—United States. 2013: 521-6.

Dong R, Chu Z, Yu F. Contriving multi-epitope subunit of vaccine for COVID-19: immunoinformatics approaches. Frontiers in Immunology. 2020 Jul; 11: 544029. doi: 10.3389/fimmu.2020.01784. DOI: https://doi.org/10.3389/fimmu.2020.01784

Ghaebi M, Osali A, Valizadeh H, Roshangar L, Ahmadi M. Vaccine development and therapeutic design for 2019‐nCoV/SARS‐CoV‐2: Challenges and chances. Journal of Cellular Physiology. 2020 Dec; 235(12): 9098-109. doi: 10.1002/jcp.29771. DOI: https://doi.org/10.1002/jcp.29771

Jyotisha, Singh S and Qureshi IA. Multi-epitope vaccine against SARS-CoV-2 applying immunoinformatics and molecular dynamics simulation approaches. Journal of Biomolecular Structure and Dynamics. 2022 May; 40(7): 2917-33. doi: 10.1080/07391102.2020.1844060. DOI: https://doi.org/10.1080/07391102.2020.1844060

Lim HX, Lim J, Jazayeri SD, Poppema S, Poh CL. Development of multi-epitope peptide-based vaccines against SARS-CoV-2. Biomedical Journal. 2021 Feb; 44(1): 18-30. doi: 10.1016/j.bj.2020.09.005. DOI: https://doi.org/10.1016/j.bj.2020.09.005

Rahman N, Ali F, Basharat Z, Shehroz M, Khan MK, Jeandet P et al.Vaccine design from the ensemble of surface glycoprotein epitopes of SARS-CoV-2: an immunoinformatics approach. Vaccines. 2020 Jul; 8(3): 423. doi: 10.3390/vaccines8030423. DOI: https://doi.org/10.3390/vaccines8030423

Sarkar B, Ullah MA, Johora FT, Taniya MA, Araf Y. Immunoinformatics-guided designing of epitope-based subunit vaccines against the SARS Coronavirus-2 (SARS-CoV-2). Immunobiology. 2020 May; 225(3): 151955. doi: 10.1016/j.imbio.2020.151955. DOI: https://doi.org/10.1016/j.imbio.2020.151955

Kar PP and Srivastava A. Immuno-informatics analysis to identify novel vaccine candidates and design of a multi-epitope based vaccine candidate against Theileria parasites. Frontiers in Immunology. 2018 Oct; 9: 340421. doi: 10.3389/fimmu.2018.02213. DOI: https://doi.org/10.3389/fimmu.2018.02213

Zawawi A, Forman R, Smith H, Mair I, Jibril M, Albaqshi MH et al. In silico design of a T-cell epitope vaccine candidate for parasitic helminth infection. PLoS Pathogens. 2020 Mar; 16(3): e1008243. doi: 10.1371/journal.ppat.1008243. DOI: https://doi.org/10.1371/journal.ppat.1008243

Tripathi NK, Shrivastava A. Recent developments in recombinant protein–based dengue vaccines. Frontiers in Immunology. 2018 Aug; 9: 408534. doi: 10.3389/fimmu.2018.01919. DOI: https://doi.org/10.3389/fimmu.2018.01919

Thomas SJ and Rothman AL. Trials and tribulations on the path to developing a dengue vaccine. Vaccine. 2015 Nov; 33: D24-31. doi: 10.1016/j.vaccine.2015.05.095. DOI: https://doi.org/10.1016/j.vaccine.2015.05.095

Thomas SJ. Preventing dengue—is the possibility now a reality?. New England Journal of Medicine. 2015 Jan; 372(2): 172-3. doi: 10.1056/NEJMe1413146. DOI: https://doi.org/10.1056/NEJMe1413146

Fadaka AO, Sibuyi NR, Martin DR, Goboza M, Klein A, Madiehe AM, Meyer M. Immunoinformatics design of a novel epitope-based vaccine candidate against dengue virus. Scientific Reports. 2021 Oct; 11(1): 19707. doi: 10.1038/s41598-021-99227-7. DOI: https://doi.org/10.1038/s41598-021-99227-7

Gupta S and Kumar A. Design of an epitope-based peptide vaccine against dengue virus isolate from eastern uttar pradesh, India. International Journal of Peptide Research and Therapeutics. 2022 Apr; 28(3): 91. doi: 10.1007/s10989-022-10402-4. DOI: https://doi.org/10.1007/s10989-022-10402-4

Verma M, Bhatnagar S, Kumari K, Mittal N, Sukhralia S, At SG, Dhanaraj PS, Lal R. Highly conserved epitopes of DENV structural and non-structural proteins: Candidates for universal vaccine targets. Gene. 2019 May; 695: 18-25. doi: 10.1016/j.gene.2019.02.001. DOI: https://doi.org/10.1016/j.gene.2019.02.001

Kar T, Narsaria U, Basak S, Deb D, Castiglione F, Mueller DM et al. A candidate multi-epitope vaccine against SARS-CoV-2. Scientific Reports. 2020 Jul; 10(1): 10895. doi: 10.1038/s41598-020-67749-1. DOI: https://doi.org/10.1038/s41598-020-67749-1