title: Manipulation of BCG vaccine: a double-edged sword.
abstract: Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach.
authors.affiliation: Section for Immunology, Department of Experimental Medical Science, Lund University, BMC D14, 22184, Lund, Sweden. vipulsingh05@gmail.com.
authors.forename: V K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow, India.
authors.forename: R
authors.initials: R
authors.lastname: Srivastava
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow, India.
authors.forename: B S
authors.initials: BS
authors.lastname: Srivastava
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D009163:Mycobacterium bovis / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D014614:Vaccines, Synthetic
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):934-9
references.pmid: 8570663
references.citation: Infect Immun. 2004 Jun;72(6):3336-43
references.pmid: 15155638
references.citation: Vaccine. 2006 Mar 6;24(10):1593-600
references.pmid: 16257099
references.citation: Immunol Cell Biol. 2003 Feb;81(1):34-45
references.pmid: 12534944
references.citation: Science. 1997 Jun 13;276(5319):1684-7
references.pmid: 9180075
references.citation: Mol Microbiol. 1999 Sep;33(6):1103-17
references.pmid: 10510226
references.citation: Mol Microbiol. 1999 May;32(3):643-55
references.pmid: 10320585
references.citation: Scand J Immunol. 2008 Feb;67(2):133-9
references.pmid: 18201368
references.citation: JAMA. 1994 Mar 2;271(9):698-702
references.pmid: 8309034
references.citation: J Clin Invest. 2005 Sep;115(9):2472-9
references.pmid: 16110326
references.citation: J Exp Med. 2008 Nov 24;205(12):2791-801
references.pmid: 18955568
references.citation: Annu Rev Immunol. 2009;27:393-422
references.pmid: 19302046
references.citation: Vaccine. 2007 Dec 21;26(1):88-95
references.pmid: 18063449
references.citation: J Clin Invest. 2011 May;121(5):1827-33
references.pmid: 21519144
references.citation: Infect Immun. 2005 Jun;73(6):3540-6
references.pmid: 15908383
references.citation: Immunity. 1995 Jun;2(6):561-72
references.pmid: 7540941
references.citation: Lancet. 1999 May 15;353(9165):1689-94
references.pmid: 10335805
references.citation: BMC Evol Biol. 2006 Nov 15;6:95
references.pmid: 17105670
references.citation: Int J Tuberc Lung Dis. 2006 Oct;10(10):1068-79
references.pmid: 17044198
references.citation: Nat Rev Urol. 2014 Mar;11(3):153-62
references.pmid: 24492433
references.citation: Annu Rev Immunol. 2013;31:475-527
references.pmid: 23516984
references.citation: Ann Natl Acad Med Sci. 1983 Jan-Mar;19(1):11-21
references.pmid: 12341889
references.citation: J Infect Dis. 1999 Mar;179(3):637-45
references.pmid: 9952370
references.citation: J Infect Dis. 2001 Aug 1;184(3):322-9
references.pmid: 11443558
references.citation: Eur J Immunol. 2000 Jun;30(6):1724-32
references.pmid: 10898510
references.citation: Mol Microbiol. 2009 Aug;73(3):325-8
references.pmid: 19602151
references.citation: Exp Parasitol. 2000 Jan;94(1):33-41
references.pmid: 10631078
references.citation: Front Immunol. 2014 Apr 07;5:152
references.pmid: 24778634
references.citation: J Immunol. 1996 Oct 15;157(8):3527-33
references.pmid: 8871652
references.citation: Vet J. 2014 Jun;200(3):362-7
references.pmid: 24792450
references.citation: Nat Med. 2003 May;9(5):533-9
references.pmid: 12692540
references.citation: Infect Immun. 1999 Apr;67(4):1702-7
references.pmid: 10085007
references.citation: J Immunol. 2011 Jun 15;186(12):7110-9
references.pmid: 21555529
references.citation: Vaccine. 2011 Jun 24;29(29-30):4754-60
references.pmid: 21565242
references.citation: DNA Cell Biol. 2009 Apr;28(4):191-9
references.pmid: 19364278
references.citation: Int Immunol. 2002 Jul;14(7):793-800
references.pmid: 12096039
references.citation: J Infect Dis. 2011 Nov 15;204(10):1573-84
references.pmid: 21933877
references.citation: Immunol Rev. 2015 Mar;264(1):46-59
references.pmid: 25703551
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13853-8
references.pmid: 11095745
references.citation: Vaccine. 2014 Feb 7;32(7):779-84
references.pmid: 24394444
references.citation: Scand J Immunol. 2005 May;61(5):410-7
references.pmid: 15882432
references.citation: Med Microbiol Immunol. 2004 Feb;193(1):19-25
references.pmid: 12905016
references.citation: Curr Opin HIV AIDS. 2012 May;7(3):268-75
references.pmid: 22495739
references.citation: Thorax. 1983 Nov;38(11):806-12
references.pmid: 6359561
references.citation: Am Rev Respir Dis. 1966 Oct;94(4):553-68
references.pmid: 5924215
references.citation: Infect Immun. 2009 Aug;77(8):3364-73
references.pmid: 19487476
references.citation: Science. 1999 May 28;284(5419):1520-3
references.pmid: 10348738
references.citation: Am J Respir Crit Care Med. 2005 Dec 15;172(12):1596-604
references.pmid: 16141443
references.citation: J Immunol. 2003 Aug 1;171(3):1602-9
references.pmid: 12874255
references.citation: Int J Med Microbiol. 2000 May;290(2):143-52
references.pmid: 11045919
references.citation: Chest. 2010 Jan;137(1):122-8
references.pmid: 19749004
references.citation: J Infect Dis. 2000 Jan;181(1):385-9
references.pmid: 10608794
references.citation: Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013-7
references.pmid: 1465432
references.citation: Vet Microbiol. 2011 Jul 5;151(1-2):14-22
references.pmid: 21420804
references.citation: J Clin Immunol. 2007 Jul;27(4):347-62
references.pmid: 17364232
references.citation: J Infect Dis. 2001 Feb 1;183(3):469-77
references.pmid: 11133379
references.citation: Vaccine. 2002 Nov 22;21(1-2):7-14
references.pmid: 12443657
references.citation: J Infect Dis. 2008 Nov 15;198(10):1491-501
references.pmid: 18808333
references.citation: Infect Immun. 2001 May;69(5):2773-8
references.pmid: 11292688
references.citation: Infect Immun. 1994 Jun;62(6):2508-14
references.pmid: 8188376
references.citation: Infect Immun. 2002 Dec;70(12):6549-57
references.pmid: 12438324
references.citation: Immunol Rev. 2015 Mar;264(1):25-45
references.pmid: 25703550
references.citation: Vaccine. 2012 Mar 30;30(16):2611-22
references.pmid: 22342705
references.citation: J Infect Dis. 2008 May 1;197(9):1263-74
references.pmid: 18422438
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12210-5
references.pmid: 11035787
references.citation: Nature. 1997 Sep 11;389(6647):133-4
references.pmid: 9296487
references.citation: Nature. 1998 Jun 11;393(6685):537-44
references.pmid: 9634230
references.citation: Ther Adv Vaccines. 2015 May;3(3):66-75
references.pmid: 26288734
references.citation: Annu Rev Immunol. 2001;19:93-129
references.pmid: 11244032
references.citation: Proc Biol Sci. 2009 Aug 22;276(1669):2987-95
references.pmid: 19493904
references.citation: Tubercle. 1981 Mar;62(1):63-8
references.pmid: 7268921
references.citation: J Immunol. 2006 Mar 15;176(6):3707-16
references.pmid: 16517739
references.citation: Nat Rev Microbiol. 2010 Sep;8(9):668-74
references.pmid: 20676146
references.citation: Infect Immun. 2000 Feb;68(2):791-5
references.pmid: 10639447
references.citation: Clin Exp Vaccine Res. 2013 Jul;2(2):83-91
references.pmid: 23858398
references.citation: Lancet Infect Dis. 2002 Feb;2(2):86-92
references.pmid: 11901655
references.citation: Lancet. 1995 Nov 18;346(8986):1339-45
references.pmid: 7475776
references.citation: Rev Infect Dis. 1989 Mar-Apr;11 Suppl 2:S353-9
references.pmid: 2652252
references.citation: Eur J Immunol. 2012 Dec;42(12):3267-79
references.pmid: 22890814
references.citation: APMIS. 2012 Jan;120(1):72-82
references.pmid: 22151310
references.citation: Clin Vaccine Immunol. 2008 May;15(5):765-72
references.pmid: 18337375
references.citation: Eur Respir J. 2011 Aug;38(2):456-64
references.pmid: 21659415
references.citation: J Immunol. 2007 Aug 15;179(4):2509-19
references.pmid: 17675513
references.citation: J Bacteriol. 1996 Mar;178(5):1274-82
references.pmid: 8631702
references.citation: Clin Exp Immunol. 2001 Feb;123(2):264-70
references.pmid: 11207657
references.citation: Vaccine. 2009 Nov 5;27(47):6495-503
references.pmid: 19720367
references.citation: J Biol Chem. 2011 May 27;286(21):19024-34
references.pmid: 21471225
references.citation: Curr Top Microbiol Immunol. 1996;215:71-96
references.pmid: 8791710
references.citation: Nat Immunol. 2009 Aug;10(8):899-906
references.pmid: 19561612
references.citation: PLoS One. 2012;7(12):e51396
references.pmid: 23251517
references.citation: Tuber Lung Dis. 2000;80(6):243-7
references.pmid: 11162765
references.citation: Vaccine. 2009 Jan 1;27(1):28-37
references.pmid: 18977269
references.citation: Clin Exp Immunol. 2000 Jan;119(1):92-8
references.pmid: 10606969
references.citation: Vaccine. 2006 Mar 15;24(12):2087-93
references.pmid: 16343704
references.citation: Infect Immun. 1997 Aug;65(8):3317-27
references.pmid: 9234793
references.citation: Infect Immun. 1999 Sep;67(9):4780-6
references.pmid: 10456931
references.citation: J Immunol. 1995 Apr 1;154(7):3359-72
references.pmid: 7897219