Safety and Immunogenicity of the H56:IC31 Tuberculosis Vaccine Candidate in Adults Successfully Treated for Drug-Susceptible Pulmonary Tuberculosis: A Phase 1 Randomized Trial

J Infect Dis. 2024 Nov 15;230(5):1262-1270. doi: 10.1093/infdis/jiae170.

Abstract

Background: H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB.

Methods: Twenty-two adults confirmed to be Mycobacterium tuberculosis negative (by 2 GeneXpert tests or 2 sputum cultures) after 4-5 months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive 2 doses of H56:IC31 (5 mg H56:500 nmol IC31; n = 16) or placebo (n = 6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity.

Results: H56:IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events or vaccine-related severe adverse events were reported. H56:IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through 6 months after the last vaccination. There was some evidence of CD8+ T-cell responses for both Ag85B and ESAT-6, but to a lesser extent than CD4+ responses.

Conclusions: H56:IC31 was associated with an acceptable safety profile, and induced a predominant CD4+ T-cell response, in adults recently treated for drug-susceptible, uncomplicated pulmonary TB.

Clinical trials registration: NCT02375698.

Keywords: H56:IC31; immunity; safety; tuberculosis; vaccine.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase I

MeSH terms

  • Acyltransferases / genetics
  • Acyltransferases / immunology
  • Adult
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Antigens, Bacterial* / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis* / immunology
  • Tuberculosis Vaccines* / administration & dosage
  • Tuberculosis Vaccines* / adverse effects
  • Tuberculosis Vaccines* / immunology
  • Tuberculosis, Pulmonary* / drug therapy
  • Tuberculosis, Pulmonary* / immunology
  • Tuberculosis, Pulmonary* / prevention & control
  • Young Adult

Substances

  • Tuberculosis Vaccines
  • Antigens, Bacterial
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • antigen 85B, Mycobacterium tuberculosis
  • Acyltransferases
  • Antibodies, Bacterial

Associated data

  • ClinicalTrials.gov/NCT02375698