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The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial

Abstract Background New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31® adjuvant. We assessed the safety and immunogenicity of... Full description

Journal Title: Vaccine 2015, Vol.33 (30), p.3592-3599
Main Author: Geldenhuys, Hennie
Other Authors: Mearns, Helen , Miles, David J.C , Tameris, Michele , Hokey, David , Shi, Zhongkai , Bennett, Sean , Andersen, Peter , Kromann, Ingrid , Hoff, Søren T , Hanekom, Willem A , Mahomed, Hassan , Hatherill, Mark , Scriba, Thomas J , van Rooyen, Michele , Bruce McClain, J , Ryall, Robert , de Bruyn, Guy
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/26048780
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title: The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial
format: Article
creator:
  • Geldenhuys, Hennie
  • Mearns, Helen
  • Miles, David J.C
  • Tameris, Michele
  • Hokey, David
  • Shi, Zhongkai
  • Bennett, Sean
  • Andersen, Peter
  • Kromann, Ingrid
  • Hoff, Søren T
  • Hanekom, Willem A
  • Mahomed, Hassan
  • Hatherill, Mark
  • Scriba, Thomas J
  • van Rooyen, Michele
  • Bruce McClain, J
  • Ryall, Robert
  • de Bruyn, Guy
subjects:
  • Adolescent
  • Adult
  • Adults
  • Allergy and Immunology
  • Antigens
  • Antigens, Bacterial - administration & dosage
  • Antigens, Bacterial - immunology
  • Antitubercular agents
  • CD4-Positive T-Lymphocytes - immunology
  • Clinical trial
  • Clinical trials
  • Cytokines - analysis
  • Deaths
  • Double-Blind Method
  • Drug Combinations
  • Enzyme-Linked Immunospot Assay
  • Female
  • H4:IC31
  • Human immunodeficiency virus
  • Humans
  • Injections, Intramuscular
  • Laboratories
  • Male
  • Microscopy
  • Middle Aged
  • Mycobacterium
  • Mycobacterium tuberculosis
  • Mycobacterium tuberculosis - immunology
  • Oligodeoxyribonucleotides - administration & dosage
  • Oligodeoxyribonucleotides - adverse effects
  • Oligopeptides - administration & dosage
  • Oligopeptides - adverse effects
  • Pharmacists
  • Placebos - administration & dosage
  • Prevention
  • South Africa
  • Staining and Labeling
  • T cells
  • The trial was registered with the South African National Clinical Trials Register (number DoH 27-1108-2525) and ClinicalTrials.gov (NCT02109874)
  • Tuberculosis
  • Tuberculosis vaccines
  • Tuberculosis Vaccines - administration & dosage
  • Tuberculosis Vaccines - adverse effects
  • Tuberculosis Vaccines - immunology
  • Urine
  • Vaccine
  • Young Adult
ispartof: Vaccine, 2015, Vol.33 (30), p.3592-3599
description: Abstract Background New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31® adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. Methods In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis -uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500 nmol IC31® , two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Results Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ+ TNF-α+ IL-2+ or TNF-α+ IL-2+ cells. These memory responses persisted up to the end of follow up, on study day 182. Conclusions H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleThe tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial
sourceAlma/SFX Local Collection
creatorGeldenhuys, Hennie ; Mearns, Helen ; Miles, David J.C ; Tameris, Michele ; Hokey, David ; Shi, Zhongkai ; Bennett, Sean ; Andersen, Peter ; Kromann, Ingrid ; Hoff, Søren T ; Hanekom, Willem A ; Mahomed, Hassan ; Hatherill, Mark ; Scriba, Thomas J ; van Rooyen, Michele ; Bruce McClain, J ; Ryall, Robert ; de Bruyn, Guy
creatorcontribGeldenhuys, Hennie ; Mearns, Helen ; Miles, David J.C ; Tameris, Michele ; Hokey, David ; Shi, Zhongkai ; Bennett, Sean ; Andersen, Peter ; Kromann, Ingrid ; Hoff, Søren T ; Hanekom, Willem A ; Mahomed, Hassan ; Hatherill, Mark ; Scriba, Thomas J ; van Rooyen, Michele ; Bruce McClain, J ; Ryall, Robert ; de Bruyn, Guy ; the H4:IC31 Trial Study Group ; H4:IC31 Trial Study Groupa ; H4:IC31 Trial Study Group
descriptionAbstract Background New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31® adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. Methods In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis -uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500 nmol IC31® , two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Results Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ+ TNF-α+ IL-2+ or TNF-α+ IL-2+ cells. These memory responses persisted up to the end of follow up, on study day 182. Conclusions H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response.
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languageeng
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subjectAdolescent ; Adult ; Adults ; Allergy and Immunology ; Antigens ; Antigens, Bacterial - administration & dosage ; Antigens, Bacterial - immunology ; Antitubercular agents ; CD4-Positive T-Lymphocytes - immunology ; Clinical trial ; Clinical trials ; Cytokines - analysis ; Deaths ; Double-Blind Method ; Drug Combinations ; Enzyme-Linked Immunospot Assay ; Female ; H4:IC31 ; Human immunodeficiency virus ; Humans ; Injections, Intramuscular ; Laboratories ; Male ; Microscopy ; Middle Aged ; Mycobacterium ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Oligodeoxyribonucleotides - administration & dosage ; Oligodeoxyribonucleotides - adverse effects ; Oligopeptides - administration & dosage ; Oligopeptides - adverse effects ; Pharmacists ; Placebos - administration & dosage ; Prevention ; South Africa ; Staining and Labeling ; T cells ; The trial was registered with the South African National Clinical Trials Register (number DoH 27-1108-2525) and ClinicalTrials.gov (NCT02109874) ; Tuberculosis ; Tuberculosis vaccines ; Tuberculosis Vaccines - administration & dosage ; Tuberculosis Vaccines - adverse effects ; Tuberculosis Vaccines - immunology ; Urine ; Vaccine ; Young Adult
ispartofVaccine, 2015, Vol.33 (30), p.3592-3599
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1Mearns, Helen
2Miles, David J.C
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7Andersen, Peter
8Kromann, Ingrid
9Hoff, Søren T
10Hanekom, Willem A
11Mahomed, Hassan
12Hatherill, Mark
13Scriba, Thomas J
14van Rooyen, Michele
15Bruce McClain, J
16Ryall, Robert
17de Bruyn, Guy
18the H4:IC31 Trial Study Group
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title
0The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial
1Vaccine
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descriptionAbstract Background New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31® adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. Methods In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis -uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500 nmol IC31® , two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Results Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ+ TNF-α+ IL-2+ or TNF-α+ IL-2+ cells. These memory responses persisted up to the end of follow up, on study day 182. Conclusions H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response.
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6Antigens, Bacterial - immunology
7Antitubercular agents
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9Clinical trial
10Clinical trials
11Cytokines - analysis
12Deaths
13Double-Blind Method
14Drug Combinations
15Enzyme-Linked Immunospot Assay
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17H4:IC31
18Human immunodeficiency virus
19Humans
20Injections, Intramuscular
21Laboratories
22Male
23Microscopy
24Middle Aged
25Mycobacterium
26Mycobacterium tuberculosis
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28Oligodeoxyribonucleotides - administration & dosage
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35South Africa
36Staining and Labeling
37T cells
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39Tuberculosis
40Tuberculosis vaccines
41Tuberculosis Vaccines - administration & dosage
42Tuberculosis Vaccines - adverse effects
43Tuberculosis Vaccines - immunology
44Urine
45Vaccine
46Young Adult
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titleThe tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial
authorGeldenhuys, Hennie ; Mearns, Helen ; Miles, David J.C ; Tameris, Michele ; Hokey, David ; Shi, Zhongkai ; Bennett, Sean ; Andersen, Peter ; Kromann, Ingrid ; Hoff, Søren T ; Hanekom, Willem A ; Mahomed, Hassan ; Hatherill, Mark ; Scriba, Thomas J ; van Rooyen, Michele ; Bruce McClain, J ; Ryall, Robert ; de Bruyn, Guy
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4Antigens
5Antigens, Bacterial - administration & dosage
6Antigens, Bacterial - immunology
7Antitubercular agents
8CD4-Positive T-Lymphocytes - immunology
9Clinical trial
10Clinical trials
11Cytokines - analysis
12Deaths
13Double-Blind Method
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20Injections, Intramuscular
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28Oligodeoxyribonucleotides - administration & dosage
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30Oligopeptides - administration & dosage
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32Pharmacists
33Placebos - administration & dosage
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35South Africa
36Staining and Labeling
37T cells
38The trial was registered with the South African National Clinical Trials Register (number DoH 27-1108-2525) and ClinicalTrials.gov (NCT02109874)
39Tuberculosis
40Tuberculosis vaccines
41Tuberculosis Vaccines - administration & dosage
42Tuberculosis Vaccines - adverse effects
43Tuberculosis Vaccines - immunology
44Urine
45Vaccine
46Young Adult
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atitleThe tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial
jtitleVaccine
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date2015
risdate2015
volume33
issue30
spage3592
epage3599
pages3592-3599
issn0264-410X
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abstractAbstract Background New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31® adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. Methods In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis -uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500 nmol IC31® , two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Results Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ+ TNF-α+ IL-2+ or TNF-α+ IL-2+ cells. These memory responses persisted up to the end of follow up, on study day 182. Conclusions H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response.
copNetherlands
pubElsevier Ltd
pmid26048780
doi10.1016/j.vaccine.2015.05.036