Mehnaj Khatoon, Madumitha B, Swati Rani, Yamini Sri S, Uma Bharathi I, Raaga R, Sagar N, Kuralayanapalya Puttahonnappa Suresh* and Sharanagouda S Patil

Spatial Epidemiology Lab, ICAR- National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, Karnataka, India

*Corresponding Author: Kuralayanapalya Puttahonnappa Suresh, Spatial Epidemiology Lab, ICAR- National Institute of Veterinary Epidemiology and Disease Informatics, Bengaluru, Karnataka, India.

Received: January 31, 2024Published: February 27, 2024

Abstract

A zoonotic Orthopoxvirus called Monkeypox Virus (MPXV) causes smallpox-like infections that affect people. Worldwide, the World Health Organization, abbreviated as WHO has been recorded to be growing in quantity of monkeypox (MPX) cases since May 2022. Currently, there are lots of problems with utilizing the smallpox vaccination to prevent monkeypox, and the treatment of infections with the disease is not clinically established. Considering this necessity and the rising number of cases of treatment resistance, creating a more potent and improved vaccination against the monkeypox virus is extremely desirable. In the present study, reverse vaccinology and several other bioinformatics and immunoinformatics tools were utilized to design multi-epitopes-based vaccine against MPXV by exploring four probable cell proteins like E8L, A28, COP-A44L and COP-B7R. The potential epitopes T-cell and B-cell were predicted from the proteins and connected with the Support of adjuvants and linkers. The predicted epitopes' physiochemical properties were evaluated, and only probable antigenic, non-allergic, and non-toxic epitopes were utilized in the multi-epitope vaccine design. The 3D structure of the designed vaccine is predicted, refined and validated for molecular docking with human immune receptor TLR4 demonstrated increased binding interaction. The designed vaccine construct was reverse transcribed and modified for E. coli strain K12 preceding inclusion inside pET28a (+) vector for its heterologous cloning and expression. Immunological responses were found to be enhanced by the IMMSIM server. In conclusion, multi-epitope vaccine candidates were created and their effectiveness has been verified. The strategy developed in this study could hold considerable importance effects on the early detection and therapy of infectious diseases brought on by the monkeypox virus.

Keywords: Immuninoformatics; Monkeypox Virus; Multi-Epitope Vaccine; Molecular Docking; In-sillico Clonning; Immune Simulation

References

1. KN Durski., et al. “Emergence of monkeypox in West Africa and Central Africa, 1970-2017/Emergence de l’orthopoxvirose simienne en Afrique de l’Ouest et en Afrique centrale, 1970-2017”. The Weekly Epidemiological Record 93 (2018): 125.
2. OJ Peter., et al. “Transmission dynamics of Monkeypox virus: a mathematical modelling approach”. Modeling Earth Systems and Environment 3 (2022): 3423-3434.
3. A Moodley., et al. “Reverse vaccinology approach to design a multi-epitope vaccine construct based on the Mycobacterium tuberculosis biomarker PE_PGRS17”. Immunologic Research 4 (2022): 501-517.
4. N Sklenovská and M Van Ranst. “Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans”. Frontiers in Public Health (2018): 1-12.
5. R Grant., et al. “Modelling human-to-human transmission of monkeypox”. World Health Organ 98.9 (2020): 638-640.
6. ME Wilson., et al. “Human monkeypox”. Clinical Infectious Diseases 2 (2014): 260-267.
7. M Naveed., et al. “Design of a novel multiple epitope-based vaccine: An immunoinformatics approach to combat SARS-CoV-2 strains”. Journal of Infection and Public Health 7 (2021): 938-946.
8. SY Ren., et al. “Monkeypox outbreak: Why is it a public health emergency of international concern? What can we do to control it?”. World Journal of Clinical Cases 30 (2022): 10873-10881.
9. ID Ladnyj., et al. “A human infection caused by monkeypox virus in Basankusu Territory, Democratic Republic of the Congo”. Bulletin of the World Health Organization 5 (1972): 593-597.
10. AK Rao., et al. “Monkeypox in a Traveler Returning from Nigeria-Dallas, Texas, July 2021”. Morbidity and Mortality Weekly Report 71.14 (2022): 509-516.
11. T Kaever., et al. “Potent Neutralization of Vaccinia Virus by Divergent Murine Antibodies Targeting a Common Site of Vulnerability in L1 Protein”. Journal of Virology 19 (2014): 11339-11355.
12. P Jeerapat. “Monkeypox: From Past to Present Outbreak”. International Journal of Current Science and Research 07 (2022): 2454-2461.
13. E Hammarlund., et al. “Multiple diagnostic techniques identify previously vaccinated individuals with protective immunity against monkeypox”. Nature Medicine9 (2005): 1005-1011.
14. PL Earl., et al. “Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox”. Nature6979 (2004): 182-185.
15. PD Yadav., et al. “First two cases of Monkeypox virus infection in travellers returned from UAE to India, July 2022”. Journal of Infection 5 (2022): e145-e148.
16. MUG Kraemer., et al. “Tracking the 2022 monkeypox outbreak with epidemiological data in real-time”. The Lancet Infectious Diseases 7 (2022): 941-942.
17. DM Pastula and KL Tyler. “An Overview of Monkeypox Virus and Its Neuroinvasive Potential”. Annals of Neurology 4 (2022): 527-531.
18. J Myers and M Maresh. “Clinical Management”. in Maternal Obesity and Pregnancy, Berlin, Heidelberg: Springer Berlin Heidelberg (2012): 43-62.
19. JW Hooper., et al. “Smallpox DNA Vaccine Protects Nonhuman Primates against Lethal Monkeypox”. Journal of Virology 9 (2004): 4433-4443.
20. Y Edghill-Smith., et al. “Modeling a Safer Smallpox Vaccination Regimen, for Human Immunodeficiency Virus Type 1-Infected Patients, in Immunocompromised Macaques”. The Journal of Infectious Diseases 8 (2003): 1181-1191.
21. SF Hoque., et al. “Scrutinizing surface glycoproteins and poxin-schlafen protein to design a heterologous recombinant vaccine against monkeypox virus”. bioRxiv (2020).
22. Y Wang., et al. “Immunogenic proteins and potential delivery platforms for mpox virus vaccine development: A rapid review”. International Journal of Biological Macromolecules 245 (2023): 125515.
23. Z Yang., et al. “An In silico deep learning approach to multi-epitope vaccine design: a SARS-CoV-2 case study”. Scientific Reports 1 (2021): 1-21.
24. S Aiman., et al. “Core genome mediated potential vaccine targets prioritization against Clostridium difficile via reverse vaccinology - an immuno-informatics approach”. Journal of Biological Research 29 (2022).
25. P Zhou., et al. “Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin”. Nature7700 (2018): 255-259.
26. S Saha and GPS Raghava. “Prediction of continuous B-cell epitopes in an antigen using recurrent neural network”. Proteins: Structure, Function, and Genetics 1 (2006): 40-48.
27. N Akhtar., et al. “Immunoinformatics-Aided Design of a Peptide Based Multiepitope Vaccine Targeting Glycoproteins and Membrane Proteins against Monkeypox Virus”. Viruses11 (2022): 2374.
28. B Reynisson., et al. “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”. Nucleic Acids Research W1 (2019): W449-W454.
29. S Fuse., et al. “Immune Responses Against Persistent Viral Infections: Possible Avenues for Immunotherapeutic Interventions”. Critical Reviews in Immunology 2 (2008): 159-183.
30. K Bhattacharya., et al. “Multi-Epitope Vaccine Design against Monkeypox Virus via Reverse Vaccinology Method Exploiting Immunoinformatic and Bioinformatic Approaches”. Vaccines12 (2022).
31. MR Wilkins., et al. “The ExPASy Server 531 53 531 Protein Identification and Analysis Tools in the ExPASy Server”. Methods in Molecular Biology 112 (1999): 531-552.
32. S Gupta., et al. “In silico Approach for Predicting Toxicity of Peptides and Proteins”. PLoS One9 (2013).
33. Z Du., et al. “The trRosetta server for fast and accurate protein structure prediction”. Nature Research (2021): 5634-5651.
34. Ç Yılmaz Çolak. “Computational Design of a Multi-epitope Vaccine Against Clostridium chauvoei: An Immunoinformatics Approach”. International Journal of Peptide Research and Therapeutics 4 (2021): 2639-2649.
35. ACB Antonelli., et al. “In silico construction of a multiepitope Zika virus vaccine using immunoinformatics tools”. Scientific Reports 1 (2022): 1-20.
36. S Aiman., et al. “Multi-epitope chimeric vaccine design against emerging Monkeypox virus via reverse vaccinology techniques- a bioinformatics and immunoinformatics approach”. Frontiers in Immunology (2022): 1-17.
37. D Kozakov., et al. “The ClusPro web server for protein-protein docking”. Nature Protocols 2 (2017): 255-278.
38. A Sarker., et al. “Evaluation of scFv protein recovery from E. coli by in vitro refolding and mild solubilization process”. Microbial Cell Factories 1 (2019): 1-12.
39. V Lennerz., et al. “Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors”. Cancer Immunology, Immunotherapy 4 (2014): 381-394.
40. C Veintimilla., et al. “The relevance of multiple clinical specimens in the diagnosis of monkeypox virus, Spain, June 2022”. Eurosurveillance 33 (2021): 1-5.
41. Y Jiao., et al. “PABPC4 Broadly Inhibits Coronavirus Replication by Degrading Nucleocapsid Protein through Selective Autophagy”. Microbiology Spectrum 2 (2021).
42. WY Zhou., et al. “Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model”. Vaccine36 (2019): 5013-5019.
43. K Naz., et al. “PanRV: Pangenome-reverse vaccinology approach for identifications of potential vaccine candidates in microbial pangenome”. BMC Bioinformatics1 (2019): 1-10.
44. Sunita N Singhvi., et al. “Computational approaches in epitope design using DNA binding proteins as vaccine candidate in Mycobacterium tuberculosis”. Infection, Genetics and Evolution 83 (2020): 104357.
45. N Khatoon., et al. “Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach”. Scientific Reports 1 (2017): 1-12.
46. A Gori., et al. “Peptides for immunological purposes: Design, strategies and applications”. Amino Acids2 (2013): 257-268.
47. R Chen. “Bacterial expression systems for recombinant protein production: coli and beyond”. Biotechnology Advances 30.5 (2012): 1102-1107.
48. T Compton., et al. “Human Cytomegalovirus Activates Inflammatory Cytokine Responses via CD14 and Toll-Like Receptor 2”. Journal of Virology 8 (2003): 4588-4596.
49. V Chauhan., et al. “Designing a multi-epitope based vaccine to combat Kaposi Sarcoma utilizing immunoinformatics approach”. Scientific Reports 1 (2019): 1-15.
50. S Arumugam and P Varamballi. “In-silico design of envelope based multi-epitope vaccine candidate against Kyasanur forest disease virus”. Scientific Reports 1 (2021): 1-15.

Citation

Citation: Kuralayanapalya Puttahonnappa Suresh., et al. “Comprehensive Epitope Prediction, Molecular Docking, and In Silico Vaccine Construction Targeting Monkeypox Virus".Acta Scientific Veterinary Sciences 6.3 (2024): 96-107.

Copyright

Copyright: © 2024 Kuralayanapalya Puttahonnappa Suresh., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.