Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial.


Journal

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
ISSN: 1469-0691
Titre abrégé: Clin Microbiol Infect
Pays: England
ID NLM: 9516420

Informations de publication

Date de publication:
Jun 2021
Historique:
received: 22 01 2020
revised: 24 08 2020
accepted: 25 08 2020
pubmed: 9 9 2020
medline: 26 8 2021
entrez: 8 9 2020
Statut: ppublish

Résumé

Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70. Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 μg (n = 25), Viaskin-PT 50 μg (n = 25), laser + Viaskin-PT 25 μg (n = 5), laser + Viaskin-PT 50 μg (n = 25)), Viaskin-placebo (n = 10) or laser + Viaskin-placebo (n = 2). Incidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser + Viaskin-PT 25 μg and 50 μg (139.87 (95% CI 87.30-224.10) and 121.76 (95% CI 95.04-156.00), respectively), than laser + Viaskin-placebo (59.49, 95% CI 39.37-89.90). Seroresponse rates were higher following laser + Viaskin-PT 25 μg (4/5 (80.0%), 95% CI 28.4-99.5) and 50 μg (22/25 (88.0%), 95% CI 68.8-97.5) than laser + Viaskin-placebo (0/12 (0.0%), 95% CI 0.0-26.5). Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boostrix®dTpa. This study is registered at ClinicalTrials.gov (NCT03035370) and was funded by DBV Technologies.

Identifiants

pubmed: 32896653
pii: S1198-743X(20)30516-4
doi: 10.1016/j.cmi.2020.08.033
pii:
doi:

Substances chimiques

Antibodies, Bacterial 0
Immunoglobulin G 0
Pertussis Toxin EC 2.4.2.31

Banques de données

ClinicalTrials.gov
['NCT03035370']

Types de publication

Clinical Trial, Phase I Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

878-885

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Auteurs

O Chatzis (O)

Centre for Vaccinology, University Hospitals of Geneva, Switzerland.

G Blanchard-Rohner (G)

Centre for Vaccinology, University Hospitals of Geneva, Switzerland; Division of General Paediatrics, Department of Paediatrics, University Hospitals of Geneva, Switzerland.

L Mondoulet (L)

DBV Technologies, Montrouge, France.

B Pelletier (B)

DBV Technologies, Montrouge, France.

A De Gea-Hominal (A)

Centre for Vaccinology, University Hospitals of Geneva, Switzerland.

M Roux (M)

DBV Technologies, Montrouge, France.

A Huttner (A)

Centre for Vaccinology, University Hospitals of Geneva, Switzerland; Division of Infectious Diseases, University Hospitals of Geneva, Switzerland.

P L Hervé (PL)

DBV Technologies, Montrouge, France.

M Rohr (M)

Division of General Paediatrics, Department of Paediatrics, University Hospitals of Geneva, Switzerland.

A Matthey (A)

Centre for Clinical Research, University Hospitals of Geneva, Switzerland.

G Gutknecht (G)

Centre for Clinical Research, University Hospitals of Geneva, Switzerland.

B Lemaître (B)

Laboratory of Vaccinology, University Hospitals of Geneva, Switzerland.

C Hayem (C)

DBV Technologies, Montrouge, France.

H T Pham (HT)

BioNet-Asia Co., Ltd, Bangkok, Thailand.

W Wijagkanalan (W)

BioNet-Asia Co., Ltd, Bangkok, Thailand.

P H Lambert (PH)

Centre for Vaccinology, University Hospitals of Geneva, Switzerland.

P H Benhamou (PH)

DBV Technologies, Montrouge, France.

C A Siegrist (CA)

Centre for Vaccinology, University Hospitals of Geneva, Switzerland; Division of General Paediatrics, Department of Paediatrics, University Hospitals of Geneva, Switzerland. Electronic address: Claire-Anne.Siegrist@unige.ch.

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Classifications MeSH