Research: Safety and immunogenicity of the novel tuberculosis vaccine ID93-GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial

24 Mar 2018
Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BC
24 Mar 2018

SATVI researchers have published an article titled: "Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial" appearing in the latest Lancet Respiratory Medicine. 

 

Background: In this randomised, double-blind, placebo-controlled phase 1 trial, we enrolled HIV-negative, previously BCG-vaccinated adults (aged 18-50 years), with no evidence of previous or current tuberculosis disease, from among community volunteers in the Worcester region of Western Cape, South Africa. Participants were randomly assigned to receive varying doses of ID93 + GLA-SE or saline placebo at day 0, day 28, and day 112. Enrolment into each cohort was sequential. Cohort 1 participants were Mycobacterium tuberculosis uninfected (as defined by negative QuantiFERON [QFT] status), and received 10 μg ID93 plus 2 μg GLA-SE, or placebo; in cohorts 2-4, QFT-negative or positive participants received escalating doses of vaccine or placebo. Cohort 2 received 2 μg ID93 plus 2 μg GLA-SE; cohort 3 received 10 μg ID93 plus 2 μg GLA-SE; and cohort 4 received 10 μg ID93 plus 5 μg GLA-SE. Dose cohort allocation was sequential; randomisation within a cohort was according to a randomly-generated sequence (3 to 1 in cohort 1, 5 to 1 in cohorts 2-4). The primary endpoint was safety of ID93 + GLA-SE as defined by solicited and unsolicited adverse events up to 28 days after each study injection and serious adverse events for the duration of the study. Specific immune responses were measured by intracellular cytokine staining, flow cytometry, and ELISA. All analyses were done according to intention to treat, with additional per-protocol analyses for immunogenicity outcomes.

Interpretation: The study found that escalating doses of ID93 + GLA-SE induced similar antigen-specific CD4-positive T cell and humoral responses, with an acceptable safety profile in BCG-immunised, M tuberculosis-infected individuals. The T-cell differentiation profiles in M tuberculosis-infected vaccinees suggest priming through natural infection. While cohort sample sizes in this phase 1 trial were small and results should be interpreted in context, these data support efficacy testing of two administrations of the lowest (2 μg) ID93 vaccine dose in tuberculosis endemic populations.

This trial is registered with ClinicalTrials.gov, number NCT01927159.

Citation: Penn-Nicholson A, Tameris M, Smit E, Day TA, Musvosvi M, Jayashankar L, Vergara J, Mabwe S, Bilek N, Geldenhuys H, Luabeya AK, Ellis R, Ginsberg AM, Hanekom WA, Reed SG, Coler RN, Scriba TJ, Hatherill M; TBVPX-114 study team.2018. Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial. Lancet Respirarory Medicine, 6(4):287-298. Click here.