Randomized, double-blind, controlled phase 1 trial of the candidate tuberculosis vaccine ChAdOx1-85A delivered by aerosol versus intramuscular route.

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, randomized, 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 1×10

FINDINGS

Both vaccination routes were well tolerated with no SAEs. Intramuscular ChAdOx1-85A was associated with more local AEs (mostly pain at 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 compartmentalization 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.

FUNDING

European Commission H2020 program (TBVAC2020 project, grant agreement 643381) via the Swiss State Secretariat for Education, Research and Innovation (SERI).

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.