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

Details

Serval ID
serval:BIB_01B38E4B14CC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Randomized, double-blind, controlled phase 1 trial of the candidate tuberculosis vaccine ChAdOx1-85A delivered by aerosol versus intramuscular route.
Journal
The Journal of infection
Author(s)
Audran R., Karoui O., Donnet L., Soumas V., Fares F., Lovis A., Noirez L., Cavassini M., Fayet-Mello A., Satti I., McShane H., Spertini F.
ISSN
1532-2742 (Electronic)
ISSN-L
0163-4453
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
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 <sup>10</sup> 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.
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.
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.
European Commission H2020 program (TBVAC2020 project, grant agreement 643381) via the Swiss State Secretariat for Education, Research and Innovation (SERI).
Keywords
Bcg, ChAdOx1-85A, Intramuscular, Tuberculosis, Vaccine, aerosol, mucosal, BCG
Pubmed
Open Access
Yes
Create date
21/06/2024 10:06
Last modification date
22/06/2024 7:08
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