Computational Design of a Novel VLP-Based Vaccine for Hepatitis B Virus.
B-Lymphocytes
/ immunology
Computational Biology
/ methods
Computer Simulation
Hepatitis B
/ immunology
Hepatitis B Vaccines
/ genetics
Hepatitis B virus
/ physiology
Humans
Immunodominant Epitopes
/ genetics
Immunoglobulin Fab Fragments
/ genetics
Molecular Dynamics Simulation
Vaccines, Virus-Like Particle
/ genetics
Viral Envelope Proteins
/ genetics
epitope
hepatitis B virus
molecular dynamics
vaccine
virus-like particles
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
04
2020
accepted:
30
07
2020
entrez:
12
10
2020
pubmed:
13
10
2020
medline:
21
5
2021
Statut:
epublish
Résumé
Hepatitis B virus (HBV) is a global virus responsible for a universal disease burden for millions of people. Various vaccination strategies have been developed using viral vector, nucleic acid, protein, peptide, and virus-like particles (VLPs) to stimulate favorable immune responses against HBV. Given the pivotal role of specific immune responses of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in infection control, we designed a VLP-based vaccine by placing the antibody-binding fragments of HBsAg in the major immunodominant region (MIR) epitope of HBcAg to stimulate multilateral immunity. A computational approach was employed to predict and evaluate the conservation, antigenicity, allergenicity, and immunogenicity of the construct. Modeling and molecular dynamics (MD) demonstrated the folding stability of HBcAg as a carrier in inserting Myrcludex and "a" determinant of HBsAg. Regions 1-50 and 118-150 of HBsAg were considered to have the highest stability to be involved in the designed vaccine. Molecular docking revealed appropriate interactions between the B cell epitope of the designed vaccine and the antibodies. Totally, the final construct was promising for inducing humoral and cellular responses against HBV.
Identifiants
pubmed: 33042118
doi: 10.3389/fimmu.2020.02074
pmc: PMC7521014
doi:
Substances chimiques
Hepatitis B Vaccines
0
Immunodominant Epitopes
0
Immunoglobulin Fab Fragments
0
L protein, hepatitis B virus
0
Vaccines, Virus-Like Particle
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2074Informations de copyright
Copyright © 2020 Mobini, Chizari, Mafakher, Rismani and Rismani.
Références
Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15016-21
pubmed: 18809920
Hepatology. 2005 Jun;41(6):1383-90
pubmed: 15915462
BMC Bioinformatics. 2005 May 31;6:132
pubmed: 15927070
Hepatology. 2009 Apr;49(4):1132-40
pubmed: 19140219
Front Immunol. 2019 Sep 20;10:2240
pubmed: 31620140
Emerg Microbes Infect. 2013 Mar;2(3):e15
pubmed: 26038456
World J Gastroenterol. 2014 May 14;20(18):5427-34
pubmed: 24833873
Proteins. 2013 Feb;81(2):229-39
pubmed: 22972754
Bioinformatics. 2005 Apr 1;21(7):951-60
pubmed: 15531603
Med Microbiol Immunol. 2015 Feb;204(1):39-55
pubmed: 25523195
J Viral Hepat. 2014 Dec;21(12):860-72
pubmed: 24498958
Bioinformatics. 2010 Dec 1;26(23):2936-43
pubmed: 20934990
Cold Spring Harb Perspect Med. 2015 May 01;5(5):a021436
pubmed: 25934462
Proteins. 2011;79 Suppl 10:147-60
pubmed: 22069036
Curr Protoc Bioinformatics. 2016 Jun 20;54:5.6.1-5.6.37
pubmed: 27322406
Cell Mol Immunol. 2019 Nov 25;:
pubmed: 31767976
Adv Enzymol Relat Areas Mol Biol. 1978;47:45-148
pubmed: 364941
Med Microbiol Immunol. 2015 Feb;204(1):57-68
pubmed: 25557605
J Immunol. 2015 Nov 15;195(10):4873-83
pubmed: 26416274
Annu Rev Immunol. 2019 Apr 26;37:457-495
pubmed: 30676822
Immunome Res. 2006 Apr 24;2:2
pubmed: 16635264
Sci Rep. 2017 Aug 15;7(1):8145
pubmed: 28811664
Proteins. 2003 Feb 15;50(3):437-50
pubmed: 12557186
J Hepatol. 2011 Jul;55(1):29-37
pubmed: 21145866
J Viral Hepat. 2005 Mar;12(2):111-24
pubmed: 15720525
Mol Cell. 1999 Jun;3(6):771-80
pubmed: 10394365
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W202-9
pubmed: 16844994
BMC Bioinformatics. 2007 Jan 05;8:4
pubmed: 17207271
Methods Enzymol. 1997;277:396-404
pubmed: 9379925
J Virol. 2007 Apr;81(8):4215-25
pubmed: 17287266
Expert Rev Vaccines. 2013 Feb;12(2):183-98
pubmed: 23414409
Aliment Pharmacol Ther. 2019 May;49(10):1346-1359
pubmed: 30982998
Viruses. 2009 Sep;1(2):185-209
pubmed: 21994545
Hepatobiliary Pancreat Dis Int. 2013 Aug;12(4):363-9
pubmed: 23924493
Nucleic Acids Res. 2017 Jul 3;45(W1):W24-W29
pubmed: 28472356
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W407-10
pubmed: 17517781
J Virol. 1985 Sep;55(3):836-9
pubmed: 2991600
Arch Virol. 2016 Oct;161(10):2765-72
pubmed: 27439498
Hum Vaccin Immunother. 2015;11(2):407-10
pubmed: 25692622
J Microbiol Biotechnol. 2018 Aug 28;28(8):1376-1383
pubmed: 30301315
Bioinformatics. 2009 May 1;25(9):1189-91
pubmed: 19151095
Vaccine. 2008 Apr 7;26(16):1972-81
pubmed: 18343539
Bioinformatics. 2012 Oct 15;28(20):2608-14
pubmed: 23053206
Proteins. 2019 Jun;87(6):520-527
pubmed: 30785653
BMC Bioinformatics. 2007 Jul 04;8:238
pubmed: 17608956
Immunology. 2009 Feb;126(2):280-9
pubmed: 18624732
J Mol Model. 2014 Jun;20(6):2278
pubmed: 24878803
Methods Enzymol. 1996;266:525-39
pubmed: 8743704
Lancet Gastroenterol Hepatol. 2019 Jul;4(7):545-558
pubmed: 30981686
Hepatology. 2018 Apr;67(4):1560-1599
pubmed: 29405329
Science. 2012 Nov 30;338(6111):1220-5
pubmed: 23197535
J Chem Inf Model. 2011 Oct 24;51(10):2778-86
pubmed: 21919503
Intervirology. 2001;44(2-3):98-114
pubmed: 11509871
Methods Mol Biol. 2014;1079:105-16
pubmed: 24170397
Expert Opin Ther Targets. 2017 Dec;21(12):1153-1159
pubmed: 29065733
Mol Biol Evol. 2016 Jul;33(7):1870-4
pubmed: 27004904
Sci Rep. 2017 May 16;7(1):1990
pubmed: 28512348
Iran J Allergy Asthma Immunol. 2015 Jun;14(3):233-45
pubmed: 26546891
FEBS Lett. 1990 Dec 10;276(1-2):172-4
pubmed: 1702393
Nucleic Acids Res. 2014 Jan;42(Database issue):D1140-6
pubmed: 24214988
J Virol. 2004 Jun;78(11):5707-19
pubmed: 15140968
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171
PLoS One. 2010 Apr 16;5(4):e9862
pubmed: 20419125
BMC Bioinformatics. 2008 Dec 02;9:514
pubmed: 19055730