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.

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.

[New puff-like disposable electronic cigarettes: expert consensus on their regulation]. / Nouvelles cigarettes électroniques jetables « puffs ¼ : consensus d'expert-e-s sur leur réglementation.

New disposable electronic cigarettes have arrived on the Swiss market since 2020. Our study, conducted according to the three steps of the Delphi fast-track approach developed at Unisanté, obtained a consensual agreement among French-speaking Switzerland experts on the regulation of these products. Ideally, the panel of experts recommends a sales ban of the product. If this is not possible, a number of aspects should be strictly regulated: taxation, product composition and marketing, and sales and consumption restrictions. These regulations should go further than the current European directive and the future Swiss law. The conclusions will be useful to support and guide political decision making from a public health and environmental perspective.

De nouvelles cigarettes électroniques jetables sont arrivées sur le marché suisse depuis 2020. Notre étude, conduite selon les trois étapes de la démarche Delphi fast-track développée à Unisanté, a obtenu un accord consensuel entre expert-e-s suisses romand-e-s sur la réglementation de ces produits. Dans l'idéal, le panel d'expert-e-s recommande une interdiction de vente du produit. Si cela n'est pas possible, certains aspects doivent être strictement réglementés : taxation, composition des produits et marketing, restrictions de vente et de consommation. Ces réglementations devraient aller plus loin que l'actuelle directive européenne et la future loi suisse. Les conclusions seront utiles pour soutenir et orienter la prise de décision politique dans une perspective de santé publique et environnementale.

Targeted drug delivery therapies inspired by natural taxes.

A taxis is the movement responding to a stimulus of an organism. This behavior helps organisms to migrate, to find food or to avoid dangers. By mimicking and using natural taxes, many bio-inspired and bio-hybrid drug delivery systems have been synthesized. Under the guidance of physical and chemical stimuli, drug-loaded carriers are led to a target, for example tumors, then locally release the drug, inducing a therapeutic effect without influencing other parts of the body. On the other hand, for moving targets, for example metastasis cancer cells or bacteria, taking advantage of their taxes behavior is a solution to capture and to eliminate them. For instance, several traps and ecological niches have been fabricated to attract cancer cells by releasing chemokines. Cancer cells are then eliminated by drug loaded inside the trap, by radiotherapy focusing on the trap location or by simply removing the trap. Further research is needed to deeply understand the taxis behavior of organisms, which is essential to ameliorate the performance of taxes-inspired drug delivery application.

Study on the hydatid cyst membrane: permeation of model molecules and interactions with drug-loaded nanoparticles.

The success of the chemotherapeutic treatment of hydatid disease is based upon the drug ability to operate on the germinal layer and on the protoscolices of the hydatid cyst interior at adequate concentrations for sufficient periods. The goal of this study was to evaluate the ability of the drug diffusion through the cyst membrane from sheep hydatid cysts and the increase of drug concentration in the cyst environment. In the first part of this work, the permeation behaviour through the hydatid cyst membrane was studied with five model molecules, having different molecular descriptors (logP, molecular weight, polar surface area ...) onto static Franz glass diffusion cells. A good correlation has been observed between the permeation coefficient and the partition coefficient, log P (r=0.951). In the second part, albendazole-loaded nanoparticles (about 300 nm) prepared by the emulsion solvent evaporation method have shown a sufficient entrapment efficiency (36.4 +/- 6.4%) to raise the apparent solubility of albendazole. The diffusion of drug from the nanoparticles across the hydatid cyst membrane was also improved compare to albendazole suspension. These results have shown the interest of the albendazole-loaded nanoparticles for the treatment of hydatid cysts in the future.