Computational formulation of a multiepitope vaccine unveils an exceptional prophylactic candidate against Merkel cell polyomavirus.
Merkel cell carcinomas (MCC)
Merkel cell polyomavirus (MCV)
immunoinformatics
molecular docking
molecular dynamics simulation (MD)
multiepitope vaccine
vaccine design
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
07
02
2023
accepted:
30
05
2023
medline:
17
7
2023
pubmed:
13
7
2023
entrez:
13
7
2023
Statut:
epublish
Résumé
Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy caused by human Merkel cell polyomavirus (MCV), leading to the most aggressive skin cancer in humans. MCV has been identified in approximately 43%-100% of MCC cases, contributing to the highly aggressive nature of primary cutaneous carcinoma and leading to a notable mortality rate. Currently, no existing vaccines or drug candidates have shown efficacy in addressing the ailment caused by this specific pathogen. Therefore, this study aimed to design a novel multiepitope vaccine candidate against the virus using integrated immunoinformatics and vaccinomics approaches. Initially, the highest antigenic, immunogenic, and non-allergenic epitopes of cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes corresponding to the virus whole protein sequences were identified and retrieved for vaccine construction. Subsequently, the selected epitopes were linked with appropriate linkers and added an adjuvant in front of the construct to enhance the immunogenicity of the vaccine candidates. Additionally, molecular docking and dynamics simulations identified strong and stable binding interactions between vaccine candidates and human Toll-like receptor 4. Furthermore, computer-aided immune simulation found the real-life-like immune response of vaccine candidates upon administration to the human body. Finally, codon optimization was conducted on the vaccine candidates to facilitate the
Identifiants
pubmed: 37441076
doi: 10.3389/fimmu.2023.1160260
pmc: PMC10333698
doi:
Substances chimiques
Vaccines
0
Viral Proteins
0
Epitopes, B-Lymphocyte
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1160260Informations de copyright
Copyright © 2023 Imon, Samad, Alam, Alsaiari, Talukder, Almehmadi, Ahammad and Mohammad.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Int J Pept Res Ther. 2021;27(3):1885-1898
pubmed: 33935610
MMWR Morb Mortal Wkly Rep. 2016 Dec 16;65(49):1405-1408
pubmed: 27977643
Nucleic Acids Res. 2013 Jul;41(Web Server issue):W384-8
pubmed: 23737448
Clin Microbiol Rev. 2004 Jul;17(3):495-508, table of contents
pubmed: 15258090
J Virol. 2010 Jul;84(14):7064-72
pubmed: 20444890
Bioinformatics. 2010 Dec 1;26(23):2936-43
pubmed: 20934990
Nucleic Acids Res. 2019 Jul 2;47(W1):W331-W337
pubmed: 31114890
Clin Dev Immunol. 2013;2013:263952
pubmed: 24489573
Nat Rev Immunol. 2018 Mar;18(3):168-182
pubmed: 29226910
BMC Med. 2023 Feb 1;21(1):36
pubmed: 36726141
Bioinformatics. 2020 Jul 1;36(13):4012-4020
pubmed: 32311016
Med Microbiol Immunol. 2019 Apr;208(2):227-238
pubmed: 30790057
Expert Rev Vaccines. 2015 Jan;14(1):21-35
pubmed: 25193104
Sci Rep. 2021 Feb 18;11(1):4049
pubmed: 33603068
BMC Biol. 2021 Feb 19;19(1):36
pubmed: 33607980
APMIS. 2013 Aug;121(8):728-45
pubmed: 23782063
Trends Mol Med. 2014 Nov;20(11):604-13
pubmed: 25263172
Clin Cancer Res. 2019 Feb 15;25(4):1185-1195
pubmed: 30093453
RSC Adv. 2021 Dec 17;11(63):40120-40135
pubmed: 35494115
Hum Vaccin Immunother. 2020 Mar 3;16(3):723-735
pubmed: 31545127
J Nephrol. 2020 Apr;33(2):343-354
pubmed: 31701375
Cancers (Basel). 2014 Jun 27;6(3):1267-97
pubmed: 24978434
Signal Transduct Target Ther. 2021 Feb 20;6(1):72
pubmed: 33608497
Nat Commun. 2023 Jan 28;14(1):464
pubmed: 36709333
Cell Host Microbe. 2013 Aug 14;14(2):125-35
pubmed: 23954152
Immunol Res. 2023 Apr 6;:
pubmed: 37022613
Bioinformatics. 2000 Apr;16(4):404-5
pubmed: 10869041
PLoS One. 2015 Jun 08;10(6):e0129476
pubmed: 26053480
Nucleic Acids Res. 1987 Feb 11;15(3):1281-95
pubmed: 3547335
CA Cancer J Clin. 2022 Jan;72(1):7-33
pubmed: 35020204
Nucleic Acids Res. 2008 Jan;36(Database issue):D190-5
pubmed: 18045787
PLoS Pathog. 2009 Sep;5(9):e1000578
pubmed: 19750217
J Natl Compr Canc Netw. 2014 Sep;12(9):1255-62
pubmed: 25190694
J Biomol Struct Dyn. 2023 May 17;:1-18
pubmed: 37194293
Adv Exp Med Biol. 2017;1018:35-56
pubmed: 29052131
BMC Bioinformatics. 2022 Feb 2;22(Suppl 14):617
pubmed: 35109785
BMC Bioinformatics. 2007 Oct 31;8:424
pubmed: 17973982
J Biochem. 1980 Dec;88(6):1895-8
pubmed: 7462208
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
pubmed: 10592235
Science. 2008 Feb 22;319(5866):1096-100
pubmed: 18202256
BMC Bioinformatics. 2008 Jan 23;9:40
pubmed: 18215316
Cancers (Basel). 2020 Jul 03;12(7):
pubmed: 32635198
BMC Bioinformatics. 2007 Jan 05;8:4
pubmed: 17207271
Bioinformation. 2011;6(7):255-61
pubmed: 21738325
J Chem Theory Comput. 2019 Mar 12;15(3):1863-1874
pubmed: 30768902
Nat Cancer. 2022 Aug;3(8):911-926
pubmed: 35999309
Sci Rep. 2017 Feb 17;7:42851
pubmed: 28211521
Sci Rep. 2022 Nov 12;12(1):19411
pubmed: 36371522
Vaccine. 2017 Jul 24;35(33):4064-4071
pubmed: 28647170
J Phys Chem A. 2019 Feb 28;123(8):1689-1699
pubmed: 30715880
Molecules. 2022 Jun 29;27(13):
pubmed: 35807415
J Clin Invest. 2011 Sep;121(9):3623-34
pubmed: 21841310
Adv Drug Deliv Rev. 2013 Oct;65(10):1357-69
pubmed: 23026637
Front Immunol. 2017 Mar 14;8:278
pubmed: 28352270
Nucleic Acids Res. 2017 Jul 3;45(W1):W24-W29
pubmed: 28472356
Methods Mol Biol. 2017;1484:255-264
pubmed: 27787831
J Chem Theory Comput. 2013 Jul 9;9(7):2887-99
pubmed: 26583973
BioDrugs. 2020 Aug;34(4):495-503
pubmed: 32447657
Pharmaceuticals (Basel). 2022 Apr 20;15(5):
pubmed: 35631328
Cell Biosci. 2013 Jul 15;3(1):29
pubmed: 23856459
Virology. 2013 Jan 5;435(1):118-30
pubmed: 23217622
Curr Oncol Rep. 2011 Dec;13(6):488-97
pubmed: 21953511
Nature. 1998 Jun 11;393(6685):537-44
pubmed: 9634230
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W407-10
pubmed: 17517781
PLoS One. 2013 Sep 13;8(9):e73957
pubmed: 24058508
Bioinformatics. 2009 Sep 1;25(17):2200-7
pubmed: 19549632
Anticancer Res. 2015 Apr;35(4):1843-9
pubmed: 25862837
PLoS Pathog. 2013;9(8):e1003558
pubmed: 23990782
Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W526-31
pubmed: 15980527
Nat Rev Immunol. 2021 Feb;21(2):83-100
pubmed: 33353987
Bioinformatics. 2014 Mar 15;30(6):846-51
pubmed: 24167156
Proteins. 2005 Sep 1;60(4):679-89
pubmed: 16021632
J Biomol Struct Dyn. 2022 Jan;40(1):14-30
pubmed: 32677533
Bioinformation. 2016 Apr 10;12(2):74-77
pubmed: 28104964
Bioinformatics. 2011 Jul 15;27(14):2013-4
pubmed: 21685045
NPJ Vaccines. 2021 Oct 5;6(1):119
pubmed: 34611173
Trends Cell Biol. 2015 Feb;25(2):74-81
pubmed: 25480024
Mar Drugs. 2021 Apr 28;19(5):
pubmed: 33925208
Hum Vaccin Immunother. 2015;11(5):1277-92
pubmed: 25751641
Int J Mol Sci. 2019 Aug 12;20(16):
pubmed: 31408949
Curr Opin Virol. 2016 Oct;20:20-27
pubmed: 27521569
Biol Direct. 2013 Dec 05;8:30
pubmed: 24304645
Molecules. 2021 Aug 17;26(16):
pubmed: 34443556
Nat Protoc. 2017 Feb;12(2):255-278
pubmed: 28079879
Vaccine. 2012 Feb 8;30(7):1322-9
pubmed: 22210138
PLoS One. 2013 Aug 05;8(8):e70166
pubmed: 23940542
Methods Mol Biol. 2007;406:89-112
pubmed: 18287689
J Immunother Cancer. 2018 Nov 20;6(1):126
pubmed: 30458852
J Virol. 2018 Jul 31;92(16):
pubmed: 29875236
Annu Rev Virol. 2020 Sep 29;7(1):289-307
pubmed: 32603631
Eur J Immunol. 2005 Aug;35(8):2295-303
pubmed: 15997466
Structure. 2020 Nov 3;28(11):1249-1258.e2
pubmed: 32857966
PLoS Comput Biol. 2013 Oct;9(10):e1003266
pubmed: 24204222
Nucleic Acids Res. 2019 Jul 2;47(W1):W502-W506
pubmed: 31114900
Viruses. 2020 Oct 12;12(10):
pubmed: 33053912
J Cutan Pathol. 2021 Mar;48(3):411-421
pubmed: 33128463
Bioinformatics. 2011 Feb 1;27(3):343-50
pubmed: 21134891
Annu Rev Med. 2019 Jan 27;70:91-104
pubmed: 30691364
Sci Rep. 2019 Feb 8;9(1):1678
pubmed: 30737447
J Am Acad Dermatol. 1991 Feb;24(2 Pt 1):198-207
pubmed: 2007664
J Hum Genet. 2009 Jan;54(1):15-39
pubmed: 19158813
Brief Bioinform. 2021 Sep 2;22(5):
pubmed: 33834183
Front Microbiol. 2017 Aug 03;8:1475
pubmed: 28824599
Int J Biol Macromol. 2021 Nov 30;191:1114-1125
pubmed: 34592225