Randomised, double-blind, controlled phase 1 trial of the candidate tuberculosis vaccine ChAdOx1-85A delivered by aerosol versus intramuscular route - 16/07/24
, François Spertini a, 1Summary |
Background |
A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A.
Methods |
We conducted a single-centre, randomised, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920). After a dose-escalation vaccination in nine BCG-vaccinated healthy adults, a dose of 1 × 1010 vp of ChAdOx1-85A was administered to twenty BCG-vaccinated adults that were randomly allocated (1:1) into two groups: aerosol ChAdOx1-85A with intramuscular saline placebo or intramuscular ChAdOx1-85A with aerosol saline placebo, using block randomisation. A control group of ten BCG-naïve adults received aerosol ChAdOx1-85A at the same dose. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 16 post-vaccination and Serious AEs (SAEs) up to 24 weeks; secondary outcomes were cell-mediated and humoral immune responses in blood and bronchoalveolar lavage (BAL) samples.
Findings |
Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at the injection site) than aerosol ChAdOx1-85A. Systemic AEs occurred in all groups, mainly fatigue and headaches, without differences between groups. Respiratory AEs were not different between BCG-vaccinated groups. Aerosol ChAdOx1-85A vaccination induced Ag85A BAL and systemic cellular immune responses with compartmentalisation of the immune responses: aerosol ChAdOx1-85A induced stronger BAL cellular responses, particularly IFNγ/IL17+CD4+ T cells; intramuscular ChAdOx1-85A induced stronger systemic cellular and humoral responses.
Interpretation |
Inhaled ChAdOx1-85A was well-tolerated and induced lung mucosal and systemic Ag85A-specific T-cell responses. These data support further evaluation of aerosol ChAdOx1-85A and other viral vectors as a BCG-booster vaccination strategy.
Le texte complet de cet article est disponible en PDF.Highlights |
• | ChAdOx1 is a candidate adenovirus-vectored TB vaccine. |
• | Aerosol ChAdOx1-85A was evaluated in Phase I for safety and immunogenicity. |
• | Aerosolized ChAdOx1-85A was safe. |
• | Aerosolized ChAdOx1-85A induced T cell responses in lung mucosa and periphery. |
Keywords : Tuberculosis, ChAdOx1-85A, Vaccine, BCG, Aerosol, Intramuscular, Mucosal
Plan
Vol 89 - N° 2
Article 106205- août 2024 Retour au numéro
Article précédent
- Surveillance of invasive pneumococcal disease in Spain exploring the impact of the COVID-19 pandemic (2019-2023)
- Covadonga Pérez-García, Julio Sempere, Sara de Miguel, Samantha Hita, Aída Úbeda, Erick Joan Vidal, Joaquín Llorente, Aurora Limia, Angel Gil de Miguel, Juan Carlos Sanz, Federico Martinón-Torres, Carmen Ardanuy, Mirian Domenech, Jose Yuste
- Long-term outcomes of patients with toxic shock syndrome: A matched cohort study
- Nathalie Auger, François M. Carrier, Jason Waechter, Émilie Brousseau, Amanda Maniraho, Aimina Ayoub, Philippe Bégin
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?