Protein Engineering: A Novel Approach in Vaccine Development
Abstract
Due to advances in biotechnology, immunology and molecular biology, protein engineering has been an innovative technique for the development, optimization and production of vaccine. Deliberate alternation in the protein structure causes the improvement or change in the properties of the protein and due to this approach modification of the antigens for inducing the strong immune response is possible thus creating a benchmark in vaccine development. Recombinant DNA Technology, Epitope Mapping, Molecular Display Systems, Fusion Proteins and Designing of virus like particles are some of the key techniques in the protein engineering. Development of the various vaccines such as Hepatitis B vaccine, HPV Vaccine and Covid-19 Vaccine are some of the successes of protein engineering approach. However, there are some challenges associated with the techniques such as Antigen Stability, Immune Evasion and High production cost. Study of structure function relationship is a crucial part of the vaccine development.
Keywords: Protein Engineering, Antigens, Recombinant DNA Technology, Epitope Mapping, Immune Evasion.
Keywords:
Protein Engineering, Antigens, Recombinant DNA Technology, Epitope Mapping, Immune EvasionDOI
https://doi.org/10.22270/jddt.v15i2.7003References
1. Fetzer S. Optimized vaccine development and manufacturing: a technology overview. Biopharm International. 2008;2008(1). https://doi.org/10.1142/9789812790958_0001
2. Adhikari D, Pokhrel S. An Overview on Protein and Peptide Drug Delivery System: Advances and Strategies. Journal of Drug Discovery and Health Sciences. 2024;1(04):239-43.
3. Ahire ED, Kshirsagar SJ. Immune responses induced by different vaccine platforms against coronavirus disease-19. Exploration of Immunology. 2021;1(4):243-57. https://doi.org/10.37349/ei.2021.00016
4. H. Tobin P, H. Richards D, A. Callender R, J. Wilson C. Protein engineering: a new frontier for biological therapeutics. Current drug metabolism. 2014;15(7):743-56. https://doi.org/10.2174/1389200216666141208151524 PMid:25495737 PMCid:PMC4931902
5. Zahradnik JM, Couch RB, Gerin JL. Safety and immunogenicity of a purified hepatitis B virus vaccine prepared by using recombinant DNA technology. Journal of Infectious Diseases. 1987;155(5):903-8. https://doi.org/10.1093/infdis/155.5.903 PMid:2951449
6. Levin A, Weiss G. Optimizing the affinity and specificity of proteins with molecular display. Molecular Biosystems. 2006;2(1):49-57. https://doi.org/10.1039/B511782H PMid:16880922
7. Deem MW, Pan K. The epitope regions of H1-subtype influenza A, with application to vaccine efficacy. Protein Engineering, Design & Selection. 2009;22(9):543-6. https://doi.org/10.1093/protein/gzp027 PMid:19578121 PMCid:PMC3307478
8. Sun H, Ma L, Wang L, Xiao P, Li H, Zhou M, et al. Research advances in hydrogen-deuterium exchange mass spectrometry for protein epitope mapping. Analytical and bioanalytical chemistry. 2021;413:2345-59. https://doi.org/10.1007/s00216-020-03091-9 PMid:33404742
9. Wu L, Barry MA. Fusion protein vectors to increase protein production and evaluate the immunogenicity of genetic vaccines. Molecular Therapy. 2000;2(3):288-97. https://doi.org/10.1006/mthe.2000.0126 PMid:10985959
10. Roldão A, Mellado MCM, Castilho LR, Carrondo MJ, Alves PM. Virus-like particles in vaccine development. Expert review of vaccines. 2010;9(10):1149-76. https://doi.org/10.1586/erv.10.115 PMid:20923267
11. Whitacre D, Peters C, Sureau C, Nio K, Li F, Su L, et al. Designing a therapeutic hepatitis B vaccine to circumvent immune tolerance. Human vaccines & immunotherapeutics. 2020;16(2):251-68. https://doi.org/10.1080/21645515.2019.1689745 PMid:31809638 PMCid:PMC7062423
12. Bai C, Wang R, Yang Q, Hao J, Zhong Q, Fan R, et al. Design and antiviral assessment of a panel of fusion proteins targeting human papillomavirus type 16. Plos one. 2024;19(10):e0311137. https://doi.org/10.1371/journal.pone.0311137 PMid:39453911 PMCid:PMC11508125
13. Li M, Wang H, Tian L, Pang Z, Yang Q, Huang T, et al. COVID-19 vaccine development: milestones, lessons and prospects. Signal transduction and targeted therapy. 2022;7(1):146. https://doi.org/10.1038/s41392-022-00996-y PMid:35504917 PMCid:PMC9062866
14. Kanekiyo M, Ellis D, King NP. New vaccine design and delivery technologies. The Journal of Infectious Diseases. 2019;219(Supplement_1):S88-S96. https://doi.org/10.1093/infdis/jiy745 PMid:30715361 PMCid:PMC6452296
15. Vishweshwaraiah YL, Dokholyan NV. Toward rational vaccine engineering. Advanced drug delivery reviews. 2022;183:114142. https://doi.org/10.1016/j.addr.2022.114142 PMid:35150769 PMCid:PMC8931536
16. Frietze KM, Peabody DS, Chackerian B. Engineering virus-like particles as vaccine platforms. Current opinion in virology. 2016;18:44-9. https://doi.org/10.1016/j.coviro.2016.03.001 PMid:27039982 PMCid:PMC4983494
17. Lestari C, Novientri G, editors. Advantages of yeast-based recombinant protein technology as vaccine products against infectious diseases. IOP Conference Series: Earth and Environmental Science; 2021: IOP Publishing. https://doi.org/10.1088/1755-1315/913/1/012099
18. Akbarian M, Chen S-H. Instability challenges and stabilization strategies of pharmaceutical proteins. Pharmaceutics. 2022;14(11):2533. https://doi.org/10.3390/pharmaceutics14112533 PMid:36432723 PMCid:PMC9699111
19. Ernst JD. Mechanisms of M. tuberculosis immune evasion as challenges to TB vaccine design. Cell host & microbe. 2018;24(1):34-42. https://doi.org/10.1016/j.chom.2018.06.004 PMid:30001523 PMCid:PMC6482466
20. Ulmer JB, Valley U, Rappuoli R. Vaccine manufacturing: challenges and solutions. Nature biotechnology. 2006;24(11):1377-83. https://doi.org/10.1038/nbt1261 PMid:17093488
21. Zolla-Pazner S, Cardozo T. Structure-function relationships of HIV-1 envelope sequence-variable regions refocus vaccine design. Nature reviews Immunology. 2010;10(7):527-35. https://doi.org/10.1038/nri2801 PMid:20577269 PMCid:PMC3167078
22. Patronov A, Doytchinova I. T-cell epitope vaccine design by immunoinformatics. Open biology. 2013;3(1):120139. https://doi.org/10.1098/rsob.120139 PMid:23303307 PMCid:PMC3603454
23. Dariushnejad H, Ghorbanzadeh V, Akbari S, Hashemzadeh P. Design of a novel recombinant multi-epitope vaccine against triple-negative breast cancer. Iranian Biomedical Journal. 2022;26(2):160.
24. Feige MJ, Buchner J. Principles and engineering of antibody folding and assembly. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics. 2014;1844(11):2024-31. https://doi.org/10.1016/j.bbapap.2014.06.004 PMid:24931831
25. Tsoras AN, Champion JA. Protein and peptide biomaterials for engineered subunit vaccines and immunotherapeutic applications. Annual Review of Chemical and Biomolecular Engineering. 2019;10(1):337-59. https://doi.org/10.1146/annurev-chembioeng-060718-030347 PMid:31173518
26. Lua LH, Connors NK, Sainsbury F, Chuan YP, Wibowo N, Middelberg AP. Bioengineering virus‐like particles as vaccines. Biotechnology and bioengineering. 2014;111(3):425-40. https://doi.org/10.1002/bit.25159 PMid:24347238
27. Borbulevych OY, Baxter TK, Yu Z, Restifo NP, Baker BM. Increased immunogenicity of an anchor-modified tumor-associated antigen is due to the enhanced stability of the peptide/MHC complex: implications for vaccine design. The Journal of Immunology. 2005;174(8):4812-20. https://doi.org/10.4049/jimmunol.174.8.4812 PMid:15814707 PMCid:PMC2241749
28. Kuriakose A, Chirmule N, Nair P. Immunogenicity of biotherapeutics: causes and association with posttranslational modifications. Journal of immunology research. 2016;2016(1):1298473. https://doi.org/10.1155/2016/1298473 PMid:27437405 PMCid:PMC4942633
29. Van Beers MM, Bardor M. Minimizing immunogenicity of biopharmaceuticals by controlling critical quality attributes of proteins. Biotechnology journal. 2012;7(12):1473-84. https://doi.org/10.1002/biot.201200065 PMid:23027660
30. Bonam SR, Partidos CD, Halmuthur SKM, Muller S. An overview of novel adjuvants designed for improving vaccine efficacy. Trends in pharmacological sciences. 2017;38(9):771-93. https://doi.org/10.1016/j.tips.2017.06.002 PMid:28668223
31. De Groot AS, Moise L, Terry F, Gutierrez AH, Hindocha P, Richard G, et al. Better epitope discovery, precision immune engineering, and accelerated vaccine design using immunoinformatics tools. Frontiers in immunology. 2020;11:442. https://doi.org/10.3389/fimmu.2020.00442 PMid:32318055 PMCid:PMC7154102
32. Xue W, Li T, Gu Y, Li S, Xia N. Molecular engineering tools for the development of vaccines against infectious diseases: current status and future directions. Expert Review of Vaccines. 2023;22(1):563-78. https://doi.org/10.1080/14760584.2023.2227699 PMid:37339445
33. Harisa GI, Faris TM, Sherif AY, Alzhrani RF, Alanazi SA, Kohaf NA, et al. Coding therapeutic nucleic acids from recombinant proteins to next-generation vaccines: Current uses, limitations, and future horizons. Molecular Biotechnology. 2024;66(8):1853-71. https://doi.org/10.1007/s12033-023-00821-z PMid:37578574
34. Cao P, Xu ZP, Li L. Tailoring functional nanoparticles for oral vaccine delivery: recent advances and future perspectives. Composites Part B: Engineering. 2022;236:109826. https://doi.org/10.1016/j.compositesb.2022.109826
35. Ellis RW. Development of combination vaccines. Vaccine. 1999;17(13-14):1635-42. https://doi.org/10.1016/S0264-410X(98)00424-1 PMid:10194816
36. Tzenios N, TAZANIOS ME, Chahine M. Combining Influenza and COVID-19 Booster Vaccination Strategy: A Systematic Review and Meta-Analysis. Available at SSRN 4276608. 2022. https://doi.org/10.2139/ssrn.4276608
37. Doolan DL, Hoffman SL. Multi-gene vaccination against malaria: a multistage, multi-immune response approach. Parasitology Today. 1997;13(5):171-8. https://doi.org/10.1016/S0169-4758(97)01040-5 PMid:15275087
38. Zhang J, Pritchard E, Hu X, Valentin T, Panilaitis B, Omenetto FG, et al. Stabilization of vaccines and antibiotics in silk and eliminating the cold chain. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(30):11981. https://doi.org/10.1073/pnas.1206210109 PMid:22778443 PMCid:PMC3409735
39. Aliahmad P, Miyake-Stoner SJ, Geall AJ, Wang NS. Next generation self-replicating RNA vectors for vaccines and immunotherapies. Cancer Gene Therapy. 2023;30(6):785-93. https://doi.org/10.1038/s41417-022-00435-8 PMid:35194198 PMCid:PMC8861484
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