Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions
Three phase II randomized trials evaluated the safety/immunogenicity of two formulations of live-attenuated tetravalent dengue virus (TDEN) vaccine in dengue-endemic (Puerto Rico, Thailand) and non-endemic (US) regions (NCT00350337/NCT00370682/NCT00468858). We describe cell-mediated immune (CMI) res...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-09-01
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| Series: | Human Vaccines & Immunotherapeutics |
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| Online Access: | http://dx.doi.org/10.1080/21645515.2019.1581536 |
| _version_ | 1797677419918786560 |
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| author | Philippe Moris Kristen M. Bauer Jeffrey R. Currier Heather Friberg Kenneth H. Eckels Ines O. Esquilin Robert V. Gibbons Bruce L. Innis Richard G. Jarman Sriluck Simasathien Peifang Sun Stephen J. Thomas Veerachai Watanaveeradej |
| author_facet | Philippe Moris Kristen M. Bauer Jeffrey R. Currier Heather Friberg Kenneth H. Eckels Ines O. Esquilin Robert V. Gibbons Bruce L. Innis Richard G. Jarman Sriluck Simasathien Peifang Sun Stephen J. Thomas Veerachai Watanaveeradej |
| author_sort | Philippe Moris |
| collection | DOAJ |
| description | Three phase II randomized trials evaluated the safety/immunogenicity of two formulations of live-attenuated tetravalent dengue virus (TDEN) vaccine in dengue-endemic (Puerto Rico, Thailand) and non-endemic (US) regions (NCT00350337/NCT00370682/NCT00468858). We describe cell-mediated immune (CMI) responses; safety and humoral responses were reported previously. Participants received two doses of vaccine or control (placebo or the precursor live-attenuated TDEN vaccine) 6 months apart. Selected US participants received a booster 5–12 months post-dose 2. Evaluated subsets of the per-protocol cohorts included 75 primarily dengue virus (DENV)-unprimed US adults, 69 primarily flavivirus-primed Thai adults, and 100 DENV-primed or DENV-unprimed Puerto Rican adults/adolescents/children. T-cell responses were quantified using intracellular cytokine staining (ICS; DENV-infected cell-lysate or DENV-1/DENV-2 peptide-pool stimulation) or IFN-γ ELISPOT (DENV-2 peptide-pool stimulation). Memory B-cell responses were quantified using B-cell ELISPOT. Across populations and age strata, DENV serotype-specific CD4+ T-cell responses were slightly to moderately increased (medians ≤0.18% [ICS]), DENV-2–biased, and variable for both formulations. Responses in unprimed subjects were primarily detected post-dose 1. Response magnitudes in primed subjects were similar between doses. Multifunctional CD8+ T-cell responses were detected after peptide-pool stimulation. T-cell responses were mostly directed to DENV nonstructural proteins 3 and 5. Memory B-cell responses were tetravalent, of low-to-moderate magnitudes (medians ≤0.25%), and mainly observed post-dose 2 in unprimed subjects and post-dose 1 in primed subjects. A third dose did not boost CMI responses. In conclusion, both formulations of the live-attenuated TDEN vaccine candidate were poorly to moderately immunogenic with respect to B-cell and T-cell responses, irrespective of the priming status of the participants. Abbreviation ATP: according-to-protocol; ICS: Intracellular Cytokine Staining; NS3: Nonstructural protein 3; ELISPOT: Enzyme-Linked ImmunoSpot; JEV: Japanese encephalitis virus; PBMC: peripheral blood mononuclear cells |
| first_indexed | 2024-03-11T22:44:57Z |
| format | Article |
| id | doaj.art-85423c0ddbfe4ec1a2141fd243dc8b6b |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:44:57Z |
| publishDate | 2019-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-85423c0ddbfe4ec1a2141fd243dc8b6b2023-09-22T08:38:26ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2019-09-011592090210510.1080/21645515.2019.15815361581536Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regionsPhilippe Moris0Kristen M. Bauer1Jeffrey R. Currier2Heather Friberg3Kenneth H. Eckels4Ines O. Esquilin5Robert V. Gibbons6Bruce L. Innis7Richard G. Jarman8Sriluck Simasathien9Peifang Sun10Stephen J. Thomas11Veerachai Watanaveeradej12GSKLandstuhl Regional Medical CenterWalter Reed Army Institute of ResearchWalter Reed Army Institute of ResearchWalter Reed Army Institute of ResearchUniversity of Puerto Rico School of MedicineU.S. Army Institute for Surgical ResearchGSKWalter Reed Army Institute of ResearchPhramongkutklao HospitalHenry Jackson Foundation for the Advancement of Military MedicineWalter Reed Army Institute of ResearchPhramongkutklao HospitalThree phase II randomized trials evaluated the safety/immunogenicity of two formulations of live-attenuated tetravalent dengue virus (TDEN) vaccine in dengue-endemic (Puerto Rico, Thailand) and non-endemic (US) regions (NCT00350337/NCT00370682/NCT00468858). We describe cell-mediated immune (CMI) responses; safety and humoral responses were reported previously. Participants received two doses of vaccine or control (placebo or the precursor live-attenuated TDEN vaccine) 6 months apart. Selected US participants received a booster 5–12 months post-dose 2. Evaluated subsets of the per-protocol cohorts included 75 primarily dengue virus (DENV)-unprimed US adults, 69 primarily flavivirus-primed Thai adults, and 100 DENV-primed or DENV-unprimed Puerto Rican adults/adolescents/children. T-cell responses were quantified using intracellular cytokine staining (ICS; DENV-infected cell-lysate or DENV-1/DENV-2 peptide-pool stimulation) or IFN-γ ELISPOT (DENV-2 peptide-pool stimulation). Memory B-cell responses were quantified using B-cell ELISPOT. Across populations and age strata, DENV serotype-specific CD4+ T-cell responses were slightly to moderately increased (medians ≤0.18% [ICS]), DENV-2–biased, and variable for both formulations. Responses in unprimed subjects were primarily detected post-dose 1. Response magnitudes in primed subjects were similar between doses. Multifunctional CD8+ T-cell responses were detected after peptide-pool stimulation. T-cell responses were mostly directed to DENV nonstructural proteins 3 and 5. Memory B-cell responses were tetravalent, of low-to-moderate magnitudes (medians ≤0.25%), and mainly observed post-dose 2 in unprimed subjects and post-dose 1 in primed subjects. A third dose did not boost CMI responses. In conclusion, both formulations of the live-attenuated TDEN vaccine candidate were poorly to moderately immunogenic with respect to B-cell and T-cell responses, irrespective of the priming status of the participants. Abbreviation ATP: according-to-protocol; ICS: Intracellular Cytokine Staining; NS3: Nonstructural protein 3; ELISPOT: Enzyme-Linked ImmunoSpot; JEV: Japanese encephalitis virus; PBMC: peripheral blood mononuclear cellshttp://dx.doi.org/10.1080/21645515.2019.1581536live-attenuated tetravalent dengue candidate vaccinecellular-mediated immune responsesdengue-primed and -unprimed populations |
| spellingShingle | Philippe Moris Kristen M. Bauer Jeffrey R. Currier Heather Friberg Kenneth H. Eckels Ines O. Esquilin Robert V. Gibbons Bruce L. Innis Richard G. Jarman Sriluck Simasathien Peifang Sun Stephen J. Thomas Veerachai Watanaveeradej Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions Human Vaccines & Immunotherapeutics live-attenuated tetravalent dengue candidate vaccine cellular-mediated immune responses dengue-primed and -unprimed populations |
| title | Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions |
| title_full | Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions |
| title_fullStr | Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions |
| title_full_unstemmed | Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions |
| title_short | Cell-mediated immune responses to different formulations of a live-attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non-endemic regions |
| title_sort | cell mediated immune responses to different formulations of a live attenuated tetravalent dengue vaccine candidate in subjects living in dengue endemic and non endemic regions |
| topic | live-attenuated tetravalent dengue candidate vaccine cellular-mediated immune responses dengue-primed and -unprimed populations |
| url | http://dx.doi.org/10.1080/21645515.2019.1581536 |
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