A Phase I/II randomized trial of H56:IC31 vaccination and adjunctive cyclooxygenase-2-inhibitor treatment in tuberculosis patients.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 11 2021
22 11 2021
Historique:
received:
18
03
2021
accepted:
25
10
2021
entrez:
23
11
2021
pubmed:
24
11
2021
medline:
29
12
2021
Statut:
epublish
Résumé
Host-directed-therapy strategies are warranted to fight tuberculosis. Here we assess the safety and immunogenicity of adjunctive vaccination with the H56:IC31 candidate and cyclooxygenase-2-inhibitor treatment (etoricoxib) in pulmonary and extra-pulmonary tuberculosis patients in a randomized open-label phase I/II clinical trial (TBCOX2, NCT02503839). A total of 222 patients were screened, 51 enrolled and randomized; 13 in the etoricoxib-group, 14 in the H56:IC31-group, 12 in the etoricoxib+H56:IC31-group and 12 controls. Three Serious Adverse Events were reported in the etoricoxib-groups; two urticarial rash and one possible disease progression, no Serious Adverse Events were vaccine related. H56:IC31 induces robust expansion of antigen-specific T-cells analyzed by fluorospot and flow cytometry, and higher proportion of seroconversions. Etoricoxib reduced H56:IC31-induced T-cell responses. Here, we show the first clinical data that H56:IC31 vaccination is safe and immunogenic in tuberculosis patients, supporting further studies of H56:IC31 as a host-directed-therapy strategy. Although etoricoxib appears safe, our data do not support therapy with adjunctive cyclooxygenase-2-inhibitors.
Identifiants
pubmed: 34811370
doi: 10.1038/s41467-021-27029-6
pii: 10.1038/s41467-021-27029-6
pmc: PMC8608791
doi:
Substances chimiques
Cyclooxygenase 2 Inhibitors
0
Tuberculosis Vaccines
0
Cyclooxygenase 2
EC 1.14.99.1
Etoricoxib
WRX4NFY03R
Banques de données
ClinicalTrials.gov
['NCT02503839']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6774Informations de copyright
© 2021. The Author(s).
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