A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults.
Adult
BCG Vaccine
/ administration & dosage
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Cytokines
/ immunology
Follow-Up Studies
Humans
Immunization, Secondary
Immunogenicity, Vaccine
Tuberculosis
/ immunology
Tuberculosis Vaccines
/ administration & dosage
United Kingdom
Vaccination
/ adverse effects
Vaccines, DNA
ChAdOx1 85A
Immunogenicity
MVA85A
Safety
Tuberculosis
Vaccine
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
22 01 2020
22 01 2020
Historique:
received:
20
06
2019
revised:
30
10
2019
accepted:
31
10
2019
pubmed:
19
11
2019
medline:
11
2
2021
entrez:
19
11
2019
Statut:
ppublish
Résumé
This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults. We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17. AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A. A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.
Sections du résumé
BACKGROUND
This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.
METHODS
We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17.
RESULTS
AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A.
CONCLUSION
A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.
Identifiants
pubmed: 31735500
pii: S0264-410X(19)31504-X
doi: 10.1016/j.vaccine.2019.10.102
pmc: PMC6985898
pii:
doi:
Substances chimiques
BCG Vaccine
0
Cytokines
0
MVA 85A
0
Tuberculosis Vaccines
0
Vaccines, DNA
0
Types de publication
Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
779-789Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
Références
Vaccine. 2013 Feb 4;31(7):1026-33
pubmed: 23266342
PLoS One. 2012;7(7):e40385
pubmed: 22808149
Lancet. 2006 Apr 8;367(9517):1173-80
pubmed: 16616560
Expert Rev Vaccines. 2007 Aug;6(4):539-46
pubmed: 17669008
N Engl J Med. 2016 Apr 28;374(17):1635-46
pubmed: 25629663
J Infect Dis. 2010 Jan 1;201(1):20-31
pubmed: 19929695
Nat Commun. 2016 Apr 12;7:11290
pubmed: 27068708
Am J Respir Crit Care Med. 2003 Dec 1;168(11):1346-52
pubmed: 12969871
Mol Ther. 2014 Mar;22(3):668-674
pubmed: 24374965
Int J Epidemiol. 1993 Dec;22(6):1154-8
pubmed: 8144299
JAMA. 1994 Mar 2;271(9):698-702
pubmed: 8309034
Lancet. 2013 Mar 23;381(9871):1021-8
pubmed: 23391465
N Engl J Med. 1996 Dec 26;335(26):1956-61
pubmed: 8960475
Microbiology. 2013 Jan;159(Pt 1):1-11
pubmed: 23175507
PLoS One. 2012;7(2):e31208
pubmed: 22363582
JAMA. 2016 Apr 19;315(15):1610-23
pubmed: 27092831
Eur J Immunol. 2007 Nov;37(11):3089-100
pubmed: 17948267
Tuberculosis (Edinb). 2016 Dec;101:102-113
pubmed: 27865379
Clin Exp Immunol. 2010 Jul 1;161(1):1-9
pubmed: 20491796
N Engl J Med. 1996 Dec 26;335(26):1941-9
pubmed: 8960473
Immunology. 2004 Jul;112(3):461-70
pubmed: 15196215
Infect Immun. 2006 Feb;74(2):1416-8
pubmed: 16428796
Nat Commun. 2013;4:2836
pubmed: 24284865
PLoS One. 2015 Nov 03;10(11):e0141687
pubmed: 26529238
Science. 1988 May 27;240(4856):1169-76
pubmed: 3131876
J Immunol. 2009 Jun 15;182(12):8047-55
pubmed: 19494330
Infect Immun. 2001 Feb;69(2):681-6
pubmed: 11159955
J Exp Med. 1993 Dec 1;178(6):2249-54
pubmed: 7504064
Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4204-8
pubmed: 10760288
Nat Med. 2007 Jul;13(7):843-50
pubmed: 17558415
N Engl J Med. 2018 Oct 25;379(17):1621-1634
pubmed: 30280651
Nat Immunol. 2007 Apr;8(4):369-77
pubmed: 17351619
J Immunol Methods. 2004 Aug;291(1-2):185-95
pubmed: 15345316
PLoS Pathog. 2009 Apr;5(4):e1000392
pubmed: 19381260
Sci Transl Med. 2015 May 06;7(286):286re5
pubmed: 25947165
Vaccine. 2015 Nov 27;33(48):6800-8
pubmed: 26478198
Tuberculosis (Edinb). 2005 Jan-Mar;85(1-2):47-52
pubmed: 15687027