Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context
Summary: Background: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic pept...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396423004887 |
| _version_ | 1797382866237128704 |
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| author | Alix Miauton Régine Audran Juliette Besson Hélène Maby-El Hajjami Maxime Karlen Loane Warpelin-Decrausaz Loredana Sene Sylvain Schaufelberger Vincent Faivre Mohamed Faouzi Mary-Anne Hartley François Spertini Blaise Genton |
| author_facet | Alix Miauton Régine Audran Juliette Besson Hélène Maby-El Hajjami Maxime Karlen Loane Warpelin-Decrausaz Loredana Sene Sylvain Schaufelberger Vincent Faivre Mohamed Faouzi Mary-Anne Hartley François Spertini Blaise Genton |
| author_sort | Alix Miauton |
| collection | DOAJ |
| description | Summary: Background: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. Methods: In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18–45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. Findings: 26 participants were enrolled (August–September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088–0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/105 CD8+, 95% CI: 0.19–5.13, p = 0.014 and +1.34/105 CD8+, 95% CI: 0.1–7.34, p = 0.024, respectively). Interpretation: Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. Funding: Emergex Vaccines Holding Limited. |
| first_indexed | 2024-03-08T21:12:32Z |
| format | Article |
| id | doaj.art-9214b3181cb140baa6e53700f23be86a |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-08T21:12:32Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-9214b3181cb140baa6e53700f23be86a2023-12-22T05:33:24ZengElsevierEBioMedicine2352-39642024-01-0199104922Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in contextAlix Miauton0Régine Audran1Juliette Besson2Hélène Maby-El Hajjami3Maxime Karlen4Loane Warpelin-Decrausaz5Loredana Sene6Sylvain Schaufelberger7Vincent Faivre8Mohamed Faouzi9Mary-Anne Hartley10François Spertini11Blaise Genton12Tropical, Travel and Vaccination Clinic, Centre for Primary Care and Public Health (Unisanté), Lausanne, Switzerland; Corresponding author. Centre for Primary Care and Public Health (Unisanté), Lausanne 1011, Switzerland.Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandTropical, Travel and Vaccination Clinic, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandClinical Trial Unit, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, SwitzerlandTropical, Travel and Vaccination Clinic, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandClinical Trial Unit, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland; Research Support Unit, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandClinical Trial Unit, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, SwitzerlandInformation Systems and Digital Transformation, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandInformation Systems and Digital Transformation, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandBiostatistics Unit, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandTropical, Travel and Vaccination Clinic, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandDivision of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, SwitzerlandTropical, Travel and Vaccination Clinic, Centre for Primary Care and Public Health (Unisanté), Lausanne, SwitzerlandSummary: Background: Vaccines that minimize the risk of vaccine-induced antibody-dependent enhancement and severe dengue are needed to address the global health threat posed by dengue. This study assessed the safety and immunogenicity of a gold nanoparticle (GNP)-based, multi-valent, synthetic peptide dengue vaccine candidate (PepGNP-Dengue), designed to provide protective CD8+ T cell immunity, without inducing antibodies. Methods: In this randomized, double-blind, vehicle-controlled, phase 1 trial (NCT04935801), healthy naïve individuals aged 18–45 years recruited at the Centre for primary care and public health, Lausanne, Switzerland, were randomly assigned to receive PepGNP-Dengue or comparator (GNP without peptides [vehicle-GNP]). Randomization was stratified into four groups (low dose [LD] and high dose [HD]), allocation was double-blind from participants and investigators. Two doses were administered by intradermal microneedle injection 21 days apart. Primary outcome was safety, secondary outcome immunogenicity. Analysis was by intention-to-treat for safety, intention-to-treat and per protocol for immunogenicity. Findings: 26 participants were enrolled (August–September 2021) to receive PepGNP-Dengue (LD or HD, n = 10 each) or vehicle-GNP (LD or HD, n = 3 each). No vaccine-related serious adverse events occurred. Most (90%) related adverse events were mild; injection site pain and transient discoloration were most frequently reported. Injection site erythema occurred in 58% of participants. As expected, PepGNP-Dengue did not elicit anti-DENV antibodies of significance. Significant increases were observed in specific CD8+ T cells and dengue dextramer+ memory cell subsets in the LD PepGNP-Dengue but not in the HD PepGNP-Dengue or vehicle-GNP groups, specifically PepGNP-activated CD137+CD69+CD8+ T cells (day 90, +0.0318%, 95% CI: 0.0088–0.1723, p = 0.046), differentiated effector memory (TemRA) and central memory (Tcm) CD8+ T cells (day 35, +0.8/105 CD8+, 95% CI: 0.19–5.13, p = 0.014 and +1.34/105 CD8+, 95% CI: 0.1–7.34, p = 0.024, respectively). Interpretation: Results provide proof of concept that a synthetic nanoparticle-based peptide vaccine can successfully induce virus-specific CD8+ T cells. The favourable safety profile and cellular responses observed support further development of PepGNP-Dengue. Funding: Emergex Vaccines Holding Limited.http://www.sciencedirect.com/science/article/pii/S2352396423004887Dengue vaccineDengue virusT cell immunityNanoparticle-based vaccine |
| spellingShingle | Alix Miauton Régine Audran Juliette Besson Hélène Maby-El Hajjami Maxime Karlen Loane Warpelin-Decrausaz Loredana Sene Sylvain Schaufelberger Vincent Faivre Mohamed Faouzi Mary-Anne Hartley François Spertini Blaise Genton Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context EBioMedicine Dengue vaccine Dengue virus T cell immunity Nanoparticle-based vaccine |
| title | Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context |
| title_full | Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context |
| title_fullStr | Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context |
| title_full_unstemmed | Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context |
| title_short | Safety and immunogenicity of a synthetic nanoparticle-based, T cell priming peptide vaccine against dengue in healthy adults in Switzerland: a double-blind, randomized, vehicle-controlled, phase 1 studyResearch in context |
| title_sort | safety and immunogenicity of a synthetic nanoparticle based t cell priming peptide vaccine against dengue in healthy adults in switzerland a double blind randomized vehicle controlled phase 1 studyresearch in context |
| topic | Dengue vaccine Dengue virus T cell immunity Nanoparticle-based vaccine |
| url | http://www.sciencedirect.com/science/article/pii/S2352396423004887 |
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