Abstract
AbstractHost-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.
Funder
same as corresponding author
Norges Forskningsråd
Ministry of Health | Statens Serum Institut
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference28 articles.
1. WHO. Global tuberculosis report 2019. (Geneva: World Health Organization, Geneva: World Health Organization, 2019).
2. Horsburgh, C. R., Barry, C. E. & Lange, C. Treat. Tuberculosis 373, 2149–2160 (2015).
3. Tiberi, S. et al. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect. Dis. https://doi.org/10.1016/s1473-3099(18)30110-5 (2018).
4. Zumla, A. et al. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. Lancet Infect. Dis. 16, e47–e63 (2016).
5. Vilaplana, C. et al. Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J. Infect. Dis. 208, 199–202 (2013).
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