H56:IC31 vaccine of no help against TB recurrence

For individuals who completed treatment for pulmonary tuberculosis (TB), vaccination with H56:IC31 does not appear to reduce the risk of disease recurrence, according to a phase 2b trial.

The trial included 831 adults (mean age 34.7 years, 72 percent male, 66 percent Black) without HIV who had completed more than 5 months of treatment for drug-susceptible pulmonary TB. These participants were randomly assigned to receive two intramuscular doses of either H56:IC31 (n=415) or placebo (n=416) in the deltoid, administered 56 days apart.

All participants were followed up until study day 421 (1 year after the second dose) and assessed at each visit for signs and symptoms of TB. If TB was suspected, two sputum samples were collected, one to be tested by automated molecular test and sent for liquid culture and the other to be stored frozen for later analysis by whole-genome sequencing (WGS). At day 421, two sputum samples were obtained from all sputum-productive participants, regardless of symptoms, to detect cases of asymptomatic TB.

The primary endpoint was culture-confirmed recurrent pulmonary TB (due to relapse with the same strain, reinfection by a different strain, or indeterminate) occurring during the period starting at day 70 (14 days after the second dose) and ending on day 421 (1 year after the second dose). Secondary endpoints included vaccine efficacy to prevent TB relapse or reinfection independently, as differentiated by WGS, and safety and immunogenicity outcomes.

In the primary modified intention-to-treat population, recurrent TB occurred in 23 of 400 participants in the H56:IC31 group and in 14 of 406 in the placebo group over a mean follow-up of 410.1 days. The corresponding vaccine efficacy was –73.8 percent (95 percent CI, –246.9 to 9.8; p=0.10) for recurrence prevention, –116.1 percent (95 percent CI, –522.2 to 16.3; p=0.11) for prevention of relapse, and –21.1 percent (95 percent CI, –245.3 to 56.5; p=0.71) for prevention of reinfection.

Two weeks after the planned second dose, H56:IC31 yielded a significant increase in the frequencies of H56-specific CD4 T cells expressing interferon-γ, tumour necrosis factor, interleukin (IL)-2, or IL-17 as compared with placebo (median percentage of CD4 T cells, 0.35 percent vs 0.11 percent; p<0.0001). H56-specific IgG responses were significantly higher in the H56:IC31 group than in the placebo group (median arbitrary units per mL, 6.84 vs 1.94; p<0.0001).

In terms of safety, mild-to-moderate injection site reactions occurred more frequently among H56:IC31 recipients than placebo recipients (40 percent vs 19 percent). There were no cases of treatment-related serious adverse events. Two participants in the H56:IC31 group and six in the placebo group died.