title: Computational tools for epitope vaccine design and evaluation.
abstract: Rational approaches will be required to develop universal vaccines for viral pathogens such as human immunodeficiency virus, hepatitis C virus, and influenza, for which empirical approaches have failed. The main objective of a rational vaccine strategy is to design novel immunogens that are capable of inducing long-term protective immunity. In practice, this requires structure-based engineering of the target neutralizing epitopes and a quantitative readout of vaccine-induced immune responses. Therefore, computational tools that can facilitate these two areas have played increasingly important roles in rational vaccine design in recent years. Here we review the computational techniques developed for protein structure prediction and antibody repertoire analysis, and demonstrate how they can be applied to the design and evaluation of epitope vaccines.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Linling
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jiang@scripps.edu.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D019295:Computational Biology / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007158:Immunologic Techniques / Q000379:methods; D015202:Protein Engineering / Q000379:methods; D014612:Vaccines / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000941:Antigens; D000939:Epitopes; D014612:Vaccines
references.citation: Proteins. 2000 Aug 15;40(3):389-408
references.pmid: 10861930
references.citation: Science. 2013 May 31;340(6136):1232910
references.pmid: 23723240
references.citation: Sci Rep. 2014;4:6778
references.pmid: 25345460
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W24-8
references.pmid: 21602266
references.citation: Annu Rev Biophys. 2008;37:289-316
references.pmid: 18573083
references.citation: Annu Rev Biochem. 2008;77:363-82
references.pmid: 18410248
references.citation: Curr Opin Struct Biol. 2010 Oct;20(5):575-83
references.pmid: 20708922
references.citation: Curr Opin Biotechnol. 2013 Dec;24(6):1089-93
references.pmid: 23481378
references.citation: Science. 2001 Oct 5;294(5540):93-6
references.pmid: 11588250
references.citation: Biol Chem. 2008 May;389(5):521-36
references.pmid: 18953718
references.citation: Curr Opin Struct Biol. 1999 Aug;9(4):509-13
references.pmid: 10449371
references.citation: Curr Opin Drug Discov Devel. 2002 Mar;5(2):251-60
references.pmid: 11926131
references.citation: Structure. 2010 Sep 8;18(9):1116-26
references.pmid: 20826338
references.citation: Curr Opin Biotechnol. 2007 Aug;18(4):305-11
references.pmid: 17644370
references.citation: Drug Discov Today. 2009 Apr;14(7-8):386-93
references.pmid: 19100336
references.citation: Annu Rev Biochem. 1997;66:549-79
references.pmid: 9242917
references.citation: Nat Immunol. 2014 Jul;15(7):589-92
references.pmid: 24940943
references.citation: Nucleic Acids Res. 2009 Jan;37(Database issue):D310-4
references.pmid: 18996897
references.citation: Nucleic Acids Res. 2005;33(7):2302-9
references.pmid: 15849316
references.citation: Protein Eng Des Sel. 2012 Oct;25(10):507-21
references.pmid: 22661385
references.citation: Science. 2010 Aug 13;329(5993):856-61
references.pmid: 20616233
references.citation: Nature. 2014 May 1;509(7498):55-62
references.pmid: 24590074
references.citation: Proteins. 2005 Feb 15;58(3):618-27
references.pmid: 15609341
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17859-60
references.pmid: 20937874
references.citation: Curr Opin Struct Biol. 2002 Aug;12(4):431-40
references.pmid: 12163064
references.citation: Bioinformatics. 2003 May 22;19(8):1015-8
references.pmid: 12761065
references.citation: Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22
references.pmid: 19920124
references.citation: Protein Sci. 2006 May;15(5):949-60
references.pmid: 16597831
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D419-25
references.pmid: 18000004
references.citation: Protein Sci. 2002 Nov;11(11):2606-21
references.pmid: 12381844
references.citation: Immunity. 2014 May 15;40(5):669-80
references.pmid: 24768348
references.citation: Nat Rev Immunol. 2011 Dec;11(12):865-72
references.pmid: 22051890
references.citation: Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):E4088-97
references.pmid: 24106303
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6470-5
references.pmid: 23536288
references.citation: Proteins. 2003;53 Suppl 6:524-33
references.pmid: 14579342
references.citation: Drug Discov Today. 2010 Aug;15(15-16):596-609
references.pmid: 20594934
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17880-7
references.pmid: 20876137
references.citation: Curr Opin Struct Biol. 1998 Aug;8(4):471-5
references.pmid: 9729739
references.citation: Bioinformatics. 2003 Aug 12;19(12):1589-91
references.pmid: 12912846
references.citation: Science. 2011 Oct 21;334(6054):373-6
references.pmid: 22021856
references.citation: Proteins. 2011 Jun;79(6):1930-9
references.pmid: 21465564
references.citation: Curr Opin Struct Biol. 2002 Aug;12(4):453-8
references.pmid: 12163067
references.citation: PLoS One. 2014;9(7):e99881
references.pmid: 24992528
references.citation: Curr Opin Struct Biol. 2010 Jun;20(3):377-84
references.pmid: 20303740
references.citation: Nature. 2014 Mar 13;507(7491):201-6
references.pmid: 24499818
references.citation: Curr Opin Biotechnol. 2009 Aug;20(4):420-8
references.pmid: 19709874
references.citation: Proteins. 2014 Feb;82 Suppl 2:112-26
references.pmid: 23780644
references.citation: Nat Protoc. 2010 Apr;5(4):725-38
references.pmid: 20360767
references.citation: Immunity. 2013 Aug 22;39(2):245-58
references.pmid: 23911655
references.citation: Mol Cell. 2005 Dec 22;20(6):811-9
references.pmid: 16364908
references.citation: Science. 2013 Dec 20;342(6165):1477-83
references.pmid: 24179159
references.citation: Protein Sci. 2003 Sep;12(9):2001-14
references.pmid: 12930999
references.citation: Curr Opin Struct Biol. 2004 Aug;14(4):487-94
references.pmid: 15313244
references.citation: Annu Rev Biophys Biomol Struct. 2000;29:291-325
references.pmid: 10940251
references.citation: Curr Opin Drug Discov Devel. 2006 Mar;9(2):251-60
references.pmid: 16566295
references.citation: Curr Comput Aided Drug Des. 2010 Apr 6;:null
references.pmid: 20402665
references.citation: Cell Rep. 2014 May 8;7(3):785-95
references.pmid: 24767986
references.citation: Drug Discov Today. 2008 Aug;13(15-16):695-701
references.pmid: 18621567
references.citation: Biotechnol Genet Eng Rev. 2010;26:1-42
references.pmid: 21415874
references.citation: Nat Biotechnol. 2012 May;30(5):423-33
references.pmid: 22565972
references.citation: J Virol. 2013 Feb;87(4):2294-306
references.pmid: 23236069
references.citation: Nat Biotechnol. 2007 Oct;25(10):1171-6
references.pmid: 17891135
references.citation: Science. 2010 Aug 13;329(5993):811-7
references.pmid: 20616231
references.citation: Methods. 2006 Sep;40(1):60-5
references.pmid: 16997714
references.citation: Science. 2011 Sep 16;333(6049):1593-602
references.pmid: 21835983
references.citation: Nat Rev Immunol. 2013 Sep;13(9):693-701
references.pmid: 23969737
references.citation: Science. 2013 Sep 13;341(6151):1199-204
references.pmid: 24031012
references.citation: Curr Opin Chem Biol. 2005 Dec;9(6):622-6
references.pmid: 16257567
references.citation: Curr Opin Struct Biol. 2006 Aug;16(4):508-13
references.pmid: 16843652
references.citation: Nucleic Acids Res. 2010 Jul;38(Web Server issue):W545-9
references.pmid: 20457744
references.citation: N Engl J Med. 2013 Feb 7;368(6):551-60
references.pmid: 23388006
references.citation: J Mol Biol. 2011 Jan 7;405(1):284-97
references.pmid: 20969873
references.citation: Methods Enzymol. 2004;383:66-93
references.pmid: 15063647
references.citation: Curr Opin Biotechnol. 2007 Dec;18(6):537-45
references.pmid: 18083549
references.citation: Nature. 2011 Dec 15;480(7377):336-43
references.pmid: 22113616
references.citation: Curr Protein Pept Sci. 2009 Jun;10(3):216-28
references.pmid: 19519452
references.citation: Front Microbiol. 2012 Sep 11;3:315
references.pmid: 23024643
references.citation: Structure. 1999 May;7(5):R105-9
references.pmid: 10378265
references.citation: Science. 2011 Nov 25;334(6059):1097-103
references.pmid: 21998254
references.citation: Nature. 2007 Feb 15;445(7129):732-7
references.pmid: 17301785
references.citation: Curr Opin Struct Biol. 2006 Apr;16(2):172-7
references.pmid: 16510277
references.citation: Curr Opin Struct Biol. 2008 Jun;18(3):342-8
references.pmid: 18436442
references.citation: Proteins. 2007;69 Suppl 8:108-17
references.pmid: 17894355
references.citation: Proteins. 2012 Aug;80(8):2080-8
references.pmid: 22522696
references.citation: Cell Mol Life Sci. 2010 Aug;67(16):2749-72
references.pmid: 20364395
references.citation: Nature. 2012 Nov 15;491(7424):406-12
references.pmid: 23151583
references.citation: Science. 2013 May 10;340(6133):711-6
references.pmid: 23539181
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9499-504
references.pmid: 22623528
references.citation: Nature. 2013 Jul 4;499(7456):102-6
references.pmid: 23698367
references.citation: Science. 2013 Dec 20;342(6165):1484-90
references.pmid: 24179160
references.citation: J Mol Biol. 2001 Aug 10;311(2):421-30
references.pmid: 11478870
references.citation: Curr Opin Immunol. 2010 Jun;22(3):358-66
references.pmid: 20299194
references.citation: Proteins. 2003 May 15;51(3):434-41
references.pmid: 12696054
references.citation: PLoS Pathog. 2013;9(11):e1003754
references.pmid: 24278016
references.citation: Curr Opin Struct Biol. 2009 Jun;19(3):341-8
references.pmid: 19481444
references.citation: BMC Bioinformatics. 2008;9:40
references.pmid: 18215316
references.citation: J Mol Biol. 2011 Jun 24;409(5):853-66
references.pmid: 21549714
references.citation: J Mol Biol. 2012 Jan 6;415(1):175-92
references.pmid: 22061265
references.citation: Nature. 2014 Oct 23;514(7523):455-61
references.pmid: 25296255
references.citation: Nat Biotechnol. 2014 Feb;32(2):158-68
references.pmid: 24441474