A Phase I/II randomized trial of H56:IC31 vaccination and adjunctive cyclooxygenase-2-inhibitor treatment in tuberculosis patients

Nat Commun. 2021 Nov 22;12(1):6774. doi: 10.1038/s41467-021-27029-6.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Etoricoxib
  • Female
  • Humans
  • Male
  • Middle Aged
  • Tuberculosis / drug therapy*
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Tuberculosis Vaccines / immunology*
  • Vaccination*
  • Young Adult


  • Cyclooxygenase 2 Inhibitors
  • Tuberculosis Vaccines
  • Cyclooxygenase 2
  • Etoricoxib

Associated data

  • ClinicalTrials.gov/NCT02503839