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.

Details

Ressource 1Download: 38128414.pdf (1077.60 [Ko])
State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_0113C1CF1BB7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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 study.
Journal
EBioMedicine
Author(s)
Miauton A., Audran R., Besson J., Maby-El Hajjami H., Karlen M., Warpelin-Decrausaz L., Sene L., Schaufelberger S., Faivre V., Faouzi M., Hartley M.A., Spertini F., Genton B.
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Publication state
Published
Issued date
01/2024
Peer-reviewed
Oui
Volume
99
Pages
104922
Language
english
Notes
Publication types: Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
Publication Status: ppublish
Abstract
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.
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.
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, +0.8/10 <sup>5</sup> CD8+, 95% CI: 0.19-5.13, p = 0.014 and +1.34/10 <sup>5</sup> CD8+, 95% CI: 0.1-7.34, p = 0.024, respectively).
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.
Emergex Vaccines Holding Limited.
Keywords
Adult, Humans, Protein Subunit Vaccines, Nanovaccines, Switzerland, Gold, Metal Nanoparticles, Vaccines, Synthetic, Antibodies, Viral, Double-Blind Method, Dengue/prevention & control, Peptides, Dengue vaccine, Dengue virus, Nanoparticle-based vaccine, T cell immunity
Pubmed
Web of science
Open Access
Yes
Create date
04/01/2024 12:02
Last modification date
10/02/2024 8:15
Usage data