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 study.
EBioMedicine
; 99: 104922, 2024 Jan.
Article
en En
| MEDLINE
| ID: mdl-38128414
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
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2_ODS3
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3_ND
Problema de salud:
1_doencas_transmissiveis
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2_cobertura_universal
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2_enfermedades_transmissibles
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3_dengue
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3_neglected_diseases
Asunto principal:
Dengue
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Nanopartículas del Metal
Límite:
Adult
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Humans
País/Región como asunto:
Europa
Idioma:
En
Revista:
EBioMedicine
Año:
2024
Tipo del documento:
Article