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Characterization of the cell-mediated immune response to Takeda’s live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting

•We characterized the T-cell responses elicited by TAK-003 against DENV non-structural proteins.•Observed CD4+ and CD8+ T-cell responses were cross-reactive and multi-functional.•Responses were observed irrespective of pre-vaccination DENV neutralizing antibodies.•CD8+ responses were of greater magn... Full description

Journal Title: Vaccine 2022-02-16, Vol.40 (8), p.1143-1151
Main Author: Tricou, Vianney
Other Authors: Gottardo, Raphael , Egan, Michael A. , Clement, Frédéric , Leroux-Roels, Geert , Sáez-Llorens, Xavier , Borkowski, Astrid , Wallace, Derek , Dean, Hansi J.
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Netherlands: Elsevier Ltd
ID: ISSN: 0264-410X
Link: https://www.ncbi.nlm.nih.gov/pubmed/35078666
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title: Characterization of the cell-mediated immune response to Takeda’s live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting
format: Article
creator:
  • Tricou, Vianney
  • Gottardo, Raphael
  • Egan, Michael A.
  • Clement, Frédéric
  • Leroux-Roels, Geert
  • Sáez-Llorens, Xavier
  • Borkowski, Astrid
  • Wallace, Derek
  • Dean, Hansi J.
subjects:
  • Adolescent
  • Adolescents
  • Antibodies
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens
  • CD4 antigen
  • CD8 antigen
  • Cell-mediated immunity
  • Clinical trials
  • Cross-reactive
  • Cross-reactivity
  • Cytokine
  • Cytokines
  • Dengue
  • Dengue - prevention & control
  • Dengue fever
  • Dengue vaccine
  • Dengue Vaccines
  • Dengue Virus
  • Disease
  • Flow cytometry
  • Humans
  • Immune response
  • Immune response (cell-mediated)
  • Immune system
  • Immunity (cell-mediated)
  • Immunity, Cellular
  • Infections
  • Interleukin 2
  • Leukocytes, Mononuclear
  • Lymphocytes
  • Lymphocytes T
  • Medical research
  • Medicine, Experimental
  • Peptides
  • Peripheral blood mononuclear cells
  • Proteins
  • Seronegative
  • Serotypes
  • T cells
  • Teenagers
  • Tumor necrosis factor-TNF
  • Tumor necrosis factor-α
  • Vaccination
  • Vaccines
  • Vaccines, Attenuated
  • Vaccines, Combined
  • Vector-borne diseases
  • Viruses
  • γ-Interferon
ispartof: Vaccine, 2022-02-16, Vol.40 (8), p.1143-1151
description: •We characterized the T-cell responses elicited by TAK-003 against DENV non-structural proteins.•Observed CD4+ and CD8+ T-cell responses were cross-reactive and multi-functional.•Responses were observed irrespective of pre-vaccination DENV neutralizing antibodies.•CD8+ responses were of greater magnitude than the CD4+ responses. As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country. Peripheral blood mononuclear cells were collected from a subset of 67 participants ≥ 10 years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov: NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-γ, TNF-α and IL-2 responses were assessed by flow cytometry. Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-γ+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-γ+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-γ + TNF-α + IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells. TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
language: eng
source:
identifier: ISSN: 0264-410X
fulltext: no_fulltext
issn:
  • 0264-410X
  • 1873-2518
url: Link


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titleCharacterization of the cell-mediated immune response to Takeda’s live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting
creatorTricou, Vianney ; Gottardo, Raphael ; Egan, Michael A. ; Clement, Frédéric ; Leroux-Roels, Geert ; Sáez-Llorens, Xavier ; Borkowski, Astrid ; Wallace, Derek ; Dean, Hansi J.
creatorcontribTricou, Vianney ; Gottardo, Raphael ; Egan, Michael A. ; Clement, Frédéric ; Leroux-Roels, Geert ; Sáez-Llorens, Xavier ; Borkowski, Astrid ; Wallace, Derek ; Dean, Hansi J.
description•We characterized the T-cell responses elicited by TAK-003 against DENV non-structural proteins.•Observed CD4+ and CD8+ T-cell responses were cross-reactive and multi-functional.•Responses were observed irrespective of pre-vaccination DENV neutralizing antibodies.•CD8+ responses were of greater magnitude than the CD4+ responses. As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country. Peripheral blood mononuclear cells were collected from a subset of 67 participants ≥ 10 years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov: NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-γ, TNF-α and IL-2 responses were assessed by flow cytometry. Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-γ+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-γ+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-γ + TNF-α + IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells. TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
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subjectAdolescent ; Adolescents ; Antibodies ; Antibodies, Neutralizing ; Antibodies, Viral ; Antigens ; CD4 antigen ; CD8 antigen ; Cell-mediated immunity ; Clinical trials ; Cross-reactive ; Cross-reactivity ; Cytokine ; Cytokines ; Dengue ; Dengue - prevention & control ; Dengue fever ; Dengue vaccine ; Dengue Vaccines ; Dengue Virus ; Disease ; Flow cytometry ; Humans ; Immune response ; Immune response (cell-mediated) ; Immune system ; Immunity (cell-mediated) ; Immunity, Cellular ; Infections ; Interleukin 2 ; Leukocytes, Mononuclear ; Lymphocytes ; Lymphocytes T ; Medical research ; Medicine, Experimental ; Peptides ; Peripheral blood mononuclear cells ; Proteins ; Seronegative ; Serotypes ; T cells ; Teenagers ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Vaccination ; Vaccines ; Vaccines, Attenuated ; Vaccines, Combined ; Vector-borne diseases ; Viruses ; γ-Interferon
ispartofVaccine, 2022-02-16, Vol.40 (8), p.1143-1151
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4Leroux-Roels, Geert
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7Wallace, Derek
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description•We characterized the T-cell responses elicited by TAK-003 against DENV non-structural proteins.•Observed CD4+ and CD8+ T-cell responses were cross-reactive and multi-functional.•Responses were observed irrespective of pre-vaccination DENV neutralizing antibodies.•CD8+ responses were of greater magnitude than the CD4+ responses. As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country. Peripheral blood mononuclear cells were collected from a subset of 67 participants ≥ 10 years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov: NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-γ, TNF-α and IL-2 responses were assessed by flow cytometry. Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-γ+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-γ+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-γ + TNF-α + IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells. TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
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0Adolescent
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2Antibodies
3Antibodies, Neutralizing
4Antibodies, Viral
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9Clinical trials
10Cross-reactive
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12Cytokine
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15Dengue - prevention & control
16Dengue fever
17Dengue vaccine
18Dengue Vaccines
19Dengue Virus
20Disease
21Flow cytometry
22Humans
23Immune response
24Immune response (cell-mediated)
25Immune system
26Immunity (cell-mediated)
27Immunity, Cellular
28Infections
29Interleukin 2
30Leukocytes, Mononuclear
31Lymphocytes
32Lymphocytes T
33Medical research
34Medicine, Experimental
35Peptides
36Peripheral blood mononuclear cells
37Proteins
38Seronegative
39Serotypes
40T cells
41Teenagers
42Tumor necrosis factor-TNF
43Tumor necrosis factor-α
44Vaccination
45Vaccines
46Vaccines, Attenuated
47Vaccines, Combined
48Vector-borne diseases
49Viruses
50γ-Interferon
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titleCharacterization of the cell-mediated immune response to Takeda’s live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting
authorTricou, Vianney ; Gottardo, Raphael ; Egan, Michael A. ; Clement, Frédéric ; Leroux-Roels, Geert ; Sáez-Llorens, Xavier ; Borkowski, Astrid ; Wallace, Derek ; Dean, Hansi J.
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1Adolescents
2Antibodies
3Antibodies, Neutralizing
4Antibodies, Viral
5Antigens
6CD4 antigen
7CD8 antigen
8Cell-mediated immunity
9Clinical trials
10Cross-reactive
11Cross-reactivity
12Cytokine
13Cytokines
14Dengue
15Dengue - prevention & control
16Dengue fever
17Dengue vaccine
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21Flow cytometry
22Humans
23Immune response
24Immune response (cell-mediated)
25Immune system
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29Interleukin 2
30Leukocytes, Mononuclear
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36Peripheral blood mononuclear cells
37Proteins
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39Serotypes
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41Teenagers
42Tumor necrosis factor-TNF
43Tumor necrosis factor-α
44Vaccination
45Vaccines
46Vaccines, Attenuated
47Vaccines, Combined
48Vector-borne diseases
49Viruses
50γ-Interferon
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7Wallace, Derek
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atitleCharacterization of the cell-mediated immune response to Takeda’s live-attenuated tetravalent dengue vaccine in adolescents participating in a phase 2 randomized controlled trial conducted in a dengue-endemic setting
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abstract•We characterized the T-cell responses elicited by TAK-003 against DENV non-structural proteins.•Observed CD4+ and CD8+ T-cell responses were cross-reactive and multi-functional.•Responses were observed irrespective of pre-vaccination DENV neutralizing antibodies.•CD8+ responses were of greater magnitude than the CD4+ responses. As robust dengue-specific CD4+ and CD8+ T cell responses are essential for protective immunity, we assessed cell-mediated immune (CMI) responses to a DENV-2-based dengue tetravalent vaccine candidate (TAK-003) in adolescents living in Panama, a dengue-endemic country. Peripheral blood mononuclear cells were collected from a subset of 67 participants ≥ 10 years old included in a phase 2 clinical trial of TAK-003 (Clinicaltrials.gov: NCT02302066). Following stimulation with dengue peptides, the frequency, magnitude, and cross-reactivity of the CD8+ and CD4+ T cell IFN-γ, TNF-α and IL-2 responses were assessed by flow cytometry. Intracellular cytokine staining identified NS1, NS3, and NS5 as the most common non-structural (NS) targets of the CD4+ T-cell response (IFN-γ+); NS3 and NS5 were the main NS targets of the CD8+ T cell response (IFN-γ+). Both CD4+ and CD8+ T-cell responses were multi-functional (IFN-γ + TNF-α + IL-2+) and cross-reactive against DENV-1, -3, and -4 serotypes. Similar responses were seen in all CMI assessments irrespective of participant baseline status for dengue neutralizing antibodies and T cells. TAK-003 elicited cross-reactive, multi-functional CD4+ and CD8+ T-cell responses, irrespective of dengue pre-exposure.
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pubElsevier Ltd
pmid35078666
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