Protective efficacy of an attenuated Mtb ΔLprG vaccine in mice.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
07
06
2020
accepted:
26
10
2020
revised:
28
12
2020
pubmed:
15
12
2020
medline:
29
1
2021
entrez:
14
12
2020
Statut:
epublish
Résumé
Bacille Calmette-Guerin (BCG), an attenuated whole cell vaccine based on Mycobacterium bovis, is the only licensed vaccine against Mycobacterium tuberculosis (Mtb), but its efficacy is suboptimal and it fails to protect against pulmonary tuberculosis. We previously reported that Mtb lacking the virulence genes lprG and rv1410c (ΔLprG) was highly attenuated in immune deficient mice. In this study, we show that attenuated ΔLprG Mtb protects C57BL/6J, Balb/cJ, and C3HeB/FeJ mice against Mtb challenge and is as attenuated as BCG in SCID mice. In C3HeB/FeJ mice, ΔLprG vaccination resulted in innate peripheral cytokine production and induced high polyclonal PPD-specific cytokine-secreting CD4+ T lymphocytes in peripheral blood. The ΔLprG vaccine afforded protective efficacy in the lungs of C3H/FeJ mice following both H37Rv and Erdman aerosolized Mtb challenges. Vaccine efficacy correlated with antigen-specific PD-1-negative CD4+ T lymphocytes as well as with serum IL-17 levels after vaccination. We hypothesize that induction of Th17 cells in lung is critical for vaccine protection, and we show a serum cytokine biomarker for IL-17 shortly after vaccination may predict protective efficacy.
Identifiants
pubmed: 33315936
doi: 10.1371/journal.ppat.1009096
pii: PPATHOGENS-D-20-01223
pmc: PMC7769599
doi:
Substances chimiques
Interleukin-17
0
Tuberculosis Vaccines
0
Vaccines, Attenuated
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009096Subventions
Organisme : NIAID NIH HHS
ID : K08 AI135098
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist. A.J.M. and D.H.B. are co-inventors on a TB vaccine patent.
Références
Lancet. 2013 Mar 23;381(9871):1021-8
pubmed: 23391465
Vaccine. 2006 Apr 24;24(17):3408-19
pubmed: 16564606
Cell Rep. 2017 Mar 14;18(11):2752-2765
pubmed: 28297677
Vaccine. 2014 Oct 14;32(45):5908-17
pubmed: 25218194
Mol Ther. 2016 Feb;24(2):398-405
pubmed: 26643797
Nat Rev Immunol. 2019 Nov;19(11):665-674
pubmed: 31570879
PLoS Pathog. 2018 Oct 12;14(10):e1007305
pubmed: 30312351
Nat Rev Microbiol. 2014 Aug;12(8):550-62
pubmed: 24998739
Immunity. 2014 Feb 20;40(2):289-302
pubmed: 24530057
mBio. 2016 May 24;7(3):
pubmed: 27222470
Dis Model Mech. 2015 Jun;8(6):603-10
pubmed: 26035868
Sci Rep. 2016 Jun 24;6:28586
pubmed: 27339100
J Immunol. 2014 Aug 15;193(4):1799-811
pubmed: 25024382
PLoS Pathog. 2014 Oct 30;10(10):e1004471
pubmed: 25356793
Lung. 2016 Jun;194(3):459-67
pubmed: 26899623
PLoS Pathog. 2014 May 15;10(5):e1004099
pubmed: 24831696
Cell Host Microbe. 2015 Nov 11;18(5):538-48
pubmed: 26607161
Nat Rev Microbiol. 2020 Jan;18(1):47-59
pubmed: 31728063
Nature. 2005 Apr 7;434(7034):767-72
pubmed: 15815631
Sci Immunol. 2016 Nov;1(5):
pubmed: 28239679
PLoS Pathog. 2016 Jan 11;12(1):e1005351
pubmed: 26751071
Nat Rev Microbiol. 2010 Apr;8(4):296-307
pubmed: 20234378
Lancet Respir Med. 2019 Sep;7(9):757-770
pubmed: 31416768
Vaccine. 2020 Feb 5;38(6):1416-1423
pubmed: 31862194
J Infect Dis. 2012 Feb 15;205(4):595-602
pubmed: 22198962
PLoS One. 2015 Sep 14;10(9):e0136500
pubmed: 26368806
J Immunol. 2014 Apr 1;192(7):2965-9
pubmed: 24591367
Clin Vaccine Immunol. 2015 Jan;22(1):91-8
pubmed: 25392011
Nat Struct Mol Biol. 2010 Sep;17(9):1088-95
pubmed: 20694006
Eur J Immunol. 2012 Feb;42(2):364-73
pubmed: 22101830
Mucosal Immunol. 2019 May;12(3):805-815
pubmed: 30778118
Vaccine. 2005 May 31;23(29):3753-61
pubmed: 15893612
Nature. 2020 Jan;577(7788):95-102
pubmed: 31894150
Nat Commun. 2017 Jul 14;8:16085
pubmed: 28706226
Lancet. 2006 Apr 8;367(9517):1173-80
pubmed: 16616560
Hum Vaccin Immunother. 2018;14(11):2692-2700
pubmed: 29913105
Mucosal Immunol. 2018 Mar;11(2):486-495
pubmed: 28853442
PLoS Comput Biol. 2017 Nov 3;13(11):e1005752
pubmed: 29099853
Dis Model Mech. 2015 Jun;8(6):591-602
pubmed: 26035867
Mucosal Immunol. 2013 Sep;6(5):972-84
pubmed: 23299616
Cell Host Microbe. 2017 Jun 14;21(6):695-706.e5
pubmed: 28618268
Cell Rep. 2018 May 01;23(5):1435-1447
pubmed: 29719256
J Exp Med. 1993 Dec 1;178(6):2249-54
pubmed: 7504064
PLoS Pathog. 2014 Sep 18;10(9):e1004376
pubmed: 25232742
J Immunol. 2014 Jun 1;192(11):5214-25
pubmed: 24778441
Mol Ther Methods Clin Dev. 2019 Feb 07;13:253-264
pubmed: 30859110
N Engl J Med. 2018 Jul 12;379(2):138-149
pubmed: 29996082
Nat Med. 2019 Feb;25(2):255-262
pubmed: 30664782
Tuberculosis (Edinb). 2010 Nov;90(6):329-32
pubmed: 20659816
Front Immunol. 2017 Oct 11;8:1252
pubmed: 29075255
Clin Vaccine Immunol. 2015 Jul;22(7):726-41
pubmed: 25924766
Mucosal Immunol. 2015 Sep;8(5):1099-109
pubmed: 25627812
Nat Rev Immunol. 2015 Aug;15(8):486-99
pubmed: 26205583
J Bacteriol. 2008 Mar;190(5):1783-91
pubmed: 18156250
PLoS Pathog. 2016 Mar 11;12(3):e1005490
pubmed: 26967901
N Engl J Med. 2018 Oct 25;379(17):1621-1634
pubmed: 30280651
Nat Immunol. 2007 Apr;8(4):369-77
pubmed: 17351619
Mucosal Immunol. 2020 Jan;13(1):140-148
pubmed: 31636345
Trends Immunol. 2014 Aug;35(8):387-95
pubmed: 24875637
Vaccine. 2013 Oct 1;31(42):4867-73
pubmed: 23965219
Cell Host Microbe. 2012 Apr 19;11(4):352-63
pubmed: 22520463
Nature. 2019 Jun;570(7762):528-532
pubmed: 31168092
PLoS Pathog. 2016 Jan 08;12(1):e1005380
pubmed: 26745507
PLoS One. 2013 Dec 12;8(12):e80579
pubmed: 24349004
Infect Immun. 2003 Oct;71(10):6004-11
pubmed: 14500521