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First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults

Abstract Background H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tub... Full description

Journal Title: Vaccine 2015, Vol.33 (33), p.4130-4140
Main Author: Luabeya, Angelique Kany Kany
Other Authors: Kagina, Benjamin M.N , Tameris, Michele D , Geldenhuys, Hennie , Hoff, Soren T , Shi, Zhongkai , Kromann, Ingrid , Hatherill, Mark , Mahomed, Hassan , Hanekom, Willem A , Andersen, Peter , Scriba, Thomas J , Schoeman, Elisma , Krohn, Colleen , Day, Cheryl L , Africa, Hadn , Makhethe, Lebohang , Smit, Erica , Brown, Yolande , Suliman, Sara , Hughes, E. Jane , Bang, Peter , Snowden, Margaret A , McClain, Bruce , Hussey, Gregory D
Format: Electronic Article Electronic Article
Language: English
Subjects:
H56
Quelle: Alma/SFX Local Collection
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/26095509
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title: First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
format: Article
creator:
  • Luabeya, Angelique Kany Kany
  • Kagina, Benjamin M.N
  • Tameris, Michele D
  • Geldenhuys, Hennie
  • Hoff, Soren T
  • Shi, Zhongkai
  • Kromann, Ingrid
  • Hatherill, Mark
  • Mahomed, Hassan
  • Hanekom, Willem A
  • Andersen, Peter
  • Scriba, Thomas J
  • Schoeman, Elisma
  • Krohn, Colleen
  • Day, Cheryl L
  • Africa, Hadn
  • Makhethe, Lebohang
  • Smit, Erica
  • Brown, Yolande
  • Suliman, Sara
  • Hughes, E. Jane
  • Bang, Peter
  • Snowden, Margaret A
  • McClain, Bruce
  • Hussey, Gregory D
subjects:
  • Acyltransferases - administration & dosage
  • Acyltransferases - immunology
  • Adolescent
  • Adult
  • Adults
  • Allergy and Immunology
  • Antibodies, Bacterial - blood
  • Antigens, Bacterial - administration & dosage
  • Antigens, Bacterial - immunology
  • Antitubercular agents
  • Bacterial Proteins - administration & dosage
  • Bacterial Proteins - immunology
  • CD4-Positive T-Lymphocytes - immunology
  • Clinical trial
  • Clinical trials
  • Cytokines - biosynthesis
  • Drug Combinations
  • Drug-Related Side Effects and Adverse Reactions - epidemiology
  • Drug-Related Side Effects and Adverse Reactions - pathology
  • Family medical history
  • Female
  • H56
  • Healthy Volunteers
  • Hematology
  • Humans
  • Infections
  • Injections, Intramuscular
  • Laboratories
  • Latent
  • Lymphocytes
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis
  • Mycobacterium tuberculosis - immunology
  • Oligodeoxyribonucleotides - administration & dosage
  • Oligopeptides - administration & dosage
  • Pain
  • Post-Exposure Prophylaxis - methods
  • Proteins
  • T-Lymphocyte Subsets - immunology
  • Treatment Outcome
  • Tuberculosis
  • Tuberculosis - prevention & control
  • Tuberculosis vaccines
  • Tuberculosis Vaccines - administration & dosage
  • Tuberculosis Vaccines - adverse effects
  • Tuberculosis Vaccines - immunology
  • Vaccine
  • Vaccines
  • Young Adult
ispartof: Vaccine, 2015, Vol.33 (33), p.4130-4140
description: Abstract Background H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tuberculosis ( M.tb ) infection. Methods Low dose (15 μg H56 protein in 500 nmol IC31) or high dose (50 μg H56, 500 nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA. Results One hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4+ T cells. M.tb -infected vaccinees had higher frequencies of H56-induced CD4+ T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ+ TNF-α+ IL-2+ ) and higher frequencies of H56-specific CD4+ T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4+ T cells, displaying a CD45RA− CCR7− effector memory phenotype, emerged after the second high-dose vaccination in M.tb -infected vaccinees. TNF-α+ IL-2+ H56-specific memory CD4+ T cells were detected mostly after low-dose H56 vaccination in M.tb -infected vaccinees, and predominantly expressed a CD45RA− CCR7+ central memory phenotype. Our results support further clinical testing of H56:IC31.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0264-410X
fulltext: fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleFirst-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
sourceAlma/SFX Local Collection
creatorLuabeya, Angelique Kany Kany ; Kagina, Benjamin M.N ; Tameris, Michele D ; Geldenhuys, Hennie ; Hoff, Soren T ; Shi, Zhongkai ; Kromann, Ingrid ; Hatherill, Mark ; Mahomed, Hassan ; Hanekom, Willem A ; Andersen, Peter ; Scriba, Thomas J ; Schoeman, Elisma ; Krohn, Colleen ; Day, Cheryl L ; Africa, Hadn ; Makhethe, Lebohang ; Smit, Erica ; Brown, Yolande ; Suliman, Sara ; Hughes, E. Jane ; Bang, Peter ; Snowden, Margaret A ; McClain, Bruce ; Hussey, Gregory D
creatorcontribLuabeya, Angelique Kany Kany ; Kagina, Benjamin M.N ; Tameris, Michele D ; Geldenhuys, Hennie ; Hoff, Soren T ; Shi, Zhongkai ; Kromann, Ingrid ; Hatherill, Mark ; Mahomed, Hassan ; Hanekom, Willem A ; Andersen, Peter ; Scriba, Thomas J ; Schoeman, Elisma ; Krohn, Colleen ; Day, Cheryl L ; Africa, Hadn ; Makhethe, Lebohang ; Smit, Erica ; Brown, Yolande ; Suliman, Sara ; Hughes, E. Jane ; Bang, Peter ; Snowden, Margaret A ; McClain, Bruce ; Hussey, Gregory D ; H56-032 Trial Study Group
descriptionAbstract Background H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tuberculosis ( M.tb ) infection. Methods Low dose (15 μg H56 protein in 500 nmol IC31) or high dose (50 μg H56, 500 nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA. Results One hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4+ T cells. M.tb -infected vaccinees had higher frequencies of H56-induced CD4+ T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ+ TNF-α+ IL-2+ ) and higher frequencies of H56-specific CD4+ T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4+ T cells, displaying a CD45RA− CCR7− effector memory phenotype, emerged after the second high-dose vaccination in M.tb -infected vaccinees. TNF-α+ IL-2+ H56-specific memory CD4+ T cells were detected mostly after low-dose H56 vaccination in M.tb -infected vaccinees, and predominantly expressed a CD45RA− CCR7+ central memory phenotype. Our results support further clinical testing of H56:IC31.
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0Luabeya, Angelique Kany Kany
1Kagina, Benjamin M.N
2Tameris, Michele D
3Geldenhuys, Hennie
4Hoff, Soren T
5Shi, Zhongkai
6Kromann, Ingrid
7Hatherill, Mark
8Mahomed, Hassan
9Hanekom, Willem A
10Andersen, Peter
11Scriba, Thomas J
12Schoeman, Elisma
13Krohn, Colleen
14Day, Cheryl L
15Africa, Hadn
16Makhethe, Lebohang
17Smit, Erica
18Brown, Yolande
19Suliman, Sara
20Hughes, E. Jane
21Bang, Peter
22Snowden, Margaret A
23McClain, Bruce
24Hussey, Gregory D
25H56-032 Trial Study Group
title
0First-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
1Vaccine
addtitleVaccine
descriptionAbstract Background H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tuberculosis ( M.tb ) infection. Methods Low dose (15 μg H56 protein in 500 nmol IC31) or high dose (50 μg H56, 500 nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA. Results One hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4+ T cells. M.tb -infected vaccinees had higher frequencies of H56-induced CD4+ T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ+ TNF-α+ IL-2+ ) and higher frequencies of H56-specific CD4+ T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4+ T cells, displaying a CD45RA− CCR7− effector memory phenotype, emerged after the second high-dose vaccination in M.tb -infected vaccinees. TNF-α+ IL-2+ H56-specific memory CD4+ T cells were detected mostly after low-dose H56 vaccination in M.tb -infected vaccinees, and predominantly expressed a CD45RA− CCR7+ central memory phenotype. Our results support further clinical testing of H56:IC31.
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0Acyltransferases - administration & dosage
1Acyltransferases - immunology
2Adolescent
3Adult
4Adults
5Allergy and Immunology
6Antibodies, Bacterial - blood
7Antigens, Bacterial - administration & dosage
8Antigens, Bacterial - immunology
9Antitubercular agents
10Bacterial Proteins - administration & dosage
11Bacterial Proteins - immunology
12CD4-Positive T-Lymphocytes - immunology
13Clinical trial
14Clinical trials
15Cytokines - biosynthesis
16Drug Combinations
17Drug-Related Side Effects and Adverse Reactions - epidemiology
18Drug-Related Side Effects and Adverse Reactions - pathology
19Family medical history
20Female
21H56
22Healthy Volunteers
23Hematology
24Humans
25Infections
26Injections, Intramuscular
27Laboratories
28Latent
29Lymphocytes
30Male
31Middle Aged
32Mycobacterium tuberculosis
33Mycobacterium tuberculosis - immunology
34Oligodeoxyribonucleotides - administration & dosage
35Oligopeptides - administration & dosage
36Pain
37Post-Exposure Prophylaxis - methods
38Proteins
39T-Lymphocyte Subsets - immunology
40Treatment Outcome
41Tuberculosis
42Tuberculosis - prevention & control
43Tuberculosis vaccines
44Tuberculosis Vaccines - administration & dosage
45Tuberculosis Vaccines - adverse effects
46Tuberculosis Vaccines - immunology
47Vaccine
48Vaccines
49Young Adult
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0Luabeya, Angelique Kany Kany
1Kagina, Benjamin M.N
2Tameris, Michele D
3Geldenhuys, Hennie
4Hoff, Soren T
5Shi, Zhongkai
6Kromann, Ingrid
7Hatherill, Mark
8Mahomed, Hassan
9Hanekom, Willem A
10Andersen, Peter
11Scriba, Thomas J
12Schoeman, Elisma
13Krohn, Colleen
14Day, Cheryl L
15Africa, Hadn
16Makhethe, Lebohang
17Smit, Erica
18Brown, Yolande
19Suliman, Sara
20Hughes, E. Jane
21Bang, Peter
22Snowden, Margaret A
23McClain, Bruce
24Hussey, Gregory D
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titleFirst-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
authorLuabeya, Angelique Kany Kany ; Kagina, Benjamin M.N ; Tameris, Michele D ; Geldenhuys, Hennie ; Hoff, Soren T ; Shi, Zhongkai ; Kromann, Ingrid ; Hatherill, Mark ; Mahomed, Hassan ; Hanekom, Willem A ; Andersen, Peter ; Scriba, Thomas J ; Schoeman, Elisma ; Krohn, Colleen ; Day, Cheryl L ; Africa, Hadn ; Makhethe, Lebohang ; Smit, Erica ; Brown, Yolande ; Suliman, Sara ; Hughes, E. Jane ; Bang, Peter ; Snowden, Margaret A ; McClain, Bruce ; Hussey, Gregory D
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7Antigens, Bacterial - administration & dosage
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9Antitubercular agents
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11Bacterial Proteins - immunology
12CD4-Positive T-Lymphocytes - immunology
13Clinical trial
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15Cytokines - biosynthesis
16Drug Combinations
17Drug-Related Side Effects and Adverse Reactions - epidemiology
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19Family medical history
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21H56
22Healthy Volunteers
23Hematology
24Humans
25Infections
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27Laboratories
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29Lymphocytes
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32Mycobacterium tuberculosis
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34Oligodeoxyribonucleotides - administration & dosage
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36Pain
37Post-Exposure Prophylaxis - methods
38Proteins
39T-Lymphocyte Subsets - immunology
40Treatment Outcome
41Tuberculosis
42Tuberculosis - prevention & control
43Tuberculosis vaccines
44Tuberculosis Vaccines - administration & dosage
45Tuberculosis Vaccines - adverse effects
46Tuberculosis Vaccines - immunology
47Vaccine
48Vaccines
49Young Adult
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22Snowden, Margaret A
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25H56-032 Trial Study Group
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0Luabeya, Angelique Kany Kany
1Kagina, Benjamin M.N
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5Shi, Zhongkai
6Kromann, Ingrid
7Hatherill, Mark
8Mahomed, Hassan
9Hanekom, Willem A
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atitleFirst-in-human trial of the post-exposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults
jtitleVaccine
addtitleVaccine
date2015
risdate2015
volume33
issue33
spage4130
epage4140
pages4130-4140
issn0264-410X
eissn1873-2518
abstractAbstract Background H56:IC31 is a candidate tuberculosis vaccine comprising a fusion protein of Ag85B, ESAT-6 and Rv2660c, formulated in IC31 adjuvant. This first-in-human, open label phase I trial assessed the safety and immunogenicity of H56:IC31 in healthy adults without or with Mycobacterium tuberculosis ( M.tb ) infection. Methods Low dose (15 μg H56 protein in 500 nmol IC31) or high dose (50 μg H56, 500 nmol IC31) vaccine was administered intramuscularly thrice, at 56-day intervals. Antigen-specific T cell responses were measured by intracellular cytokine staining and antibody responses by ELISA. Results One hundred and twenty-six subjects were screened and 25 enrolled and vaccinated. No serious adverse events were reported. Nine subjects (36%) presented with transient cardiovascular adverse events. The H56:IC31 vaccine induced antigen-specific IgG responses and Th1 cytokine-expressing CD4+ T cells. M.tb -infected vaccinees had higher frequencies of H56-induced CD4+ T cells than uninfected vaccinees. Low dose vaccination induced more polyfunctional (IFN-γ+ TNF-α+ IL-2+ ) and higher frequencies of H56-specific CD4+ T cells compared with high dose vaccination. A striking increase in IFN-γ-only-expressing CD4+ T cells, displaying a CD45RA− CCR7− effector memory phenotype, emerged after the second high-dose vaccination in M.tb -infected vaccinees. TNF-α+ IL-2+ H56-specific memory CD4+ T cells were detected mostly after low-dose H56 vaccination in M.tb -infected vaccinees, and predominantly expressed a CD45RA− CCR7+ central memory phenotype. Our results support further clinical testing of H56:IC31.
copNetherlands
pubElsevier Ltd
pmid26095509
doi10.1016/j.vaccine.2015.06.051