# Tuberculosis Vaccines: An Update of Recent and Ongoing Clinical Trials
## 3 TB Novel Vaccines
### TB Subunit Vaccines
#### 3.1.5 ID93 + GLA-SE  
Over the last half decade, much research has also been conducted on ID93+GLA-SE. This is a subunit vaccine comprising four antigens representing different families of _M. tuberculosis_ proteins. These proteins include two predicted outer membrane proteins, Rv1813 and Rv2608, and two secreted proteins, Rv3619 and Rv3620, belonging to the ESAT-6 family [(17)]. In combination with these is the Th1-inducing synthetic TLR4-agonist adjuvant, Glucopyranoside Lipid A (GLA), formulated in a stable oil-in-water nanemulsion (SE) [(12; 17)]. In animal models, this vaccine demonstrated prophylactic and therapeutic immunization potential and, ultimately, human trials followed thereafter [(17)]. A randomized double-blind placebo-controlled phase I trial to assess the safety and immunogenicity of ID93+GLA-SE in healthy BCG-vaccinated adults was completed in 2015 (ClinicalTrials.gov: NCT01927159). This trial enrolled 66 healthy HIV-adults, with an average age of 25 years, who were randomly assigned to five groups: one placebo and four cohorts, with varying doses of the vaccine [(18)]. Following randomization, the study population was divided as follows: the placebo group (saline, \(n=12\)); Cohort 1 (ID93 (10 \(\upmu\)g) + GLA-SE (2 \(\upmu\)g, \(n=9\)); Cohort 2 (2 \(\upmu\)g ID93 + 2 \(\upmu\)g GLA-SE, \(n=15\)); Cohort 3 (10 \(\upmu\)g ID93 + 2 \(\upmu\)g GLA-SE, \(n=15\)); and Cohort 4 (10 \(\upmu\)g ID93 + 5 \(\upmu\)g GLA-SE, \(n=15\)) [(18)]. On days 0, 28, and 112, participants were injected intramuscularly as per their enrolled cohort [(18)]. All participants were followed over a six-month period, and injection site reaction and AEs were assessed at days 1, 3, 7, 14, and 28 after each injection [(18)]. Antibodies and T cell responses were also measured [(18)]. The AEs reported were mild or moderate in nature, with no SAEs in the vaccine groups [(18)]. In assessing vaccine-induced immunogenicity, ID93+GLA-SE vaccination induced marked rapid increases in the frequencies of total cytokine-expressing CD4+ T cells specific to Rv1813, Rv2608, Rv3619, and Rv3620 in all four cohorts [(18)]. ID93-specific IgG responses also increased significantly after the three ID93+GLA-SE vaccinations in participants from all four cohorts, with levels maintainedabove those of prevaccination, and of those in the placebo recipients at the end of the study [18]. Humoral responses were also detected against all four antigens specifically dominated by IgG1 and IgG3 [18]. A further phase I randomized double-blind clinical trial was completed in which the safety, tolerability, and immunogenicity of ID93+GLA-SE was evaluated (ClinicalTrials.gov: NCT02508376). While no results have been released yet, this study differed in that ID93 was administered alone and in combination with GLA-SE, as well as in combination with the AP10-60 adjuvant. Recently, a phase I clinical trial evaluating the safety, immunogenicity, and tolerability of ID93+GLA-SE in adults (ClinicalTrials.gov: NCT03722472) was completed, with the results yet to be posted. A similar clinical trial evaluating the same parameters, but in adolescents and in the phase II stage (ClinicalTrials.gov: NCT03806686), is underway. Further clinical trials have also progressed to phase II. A triple-blind phase IIa clinical trial in TB patients following completion of treatment has been conducted (ClinicalTrials.gov: NCT02465216). After enrolment and randomized allocation, 60 participants were divided into four groups with differing doses of antigen and adjuvant: Group 1: low-dose antigen and adjuvant; Group 2: high-dose antigen, low-dose adjuvant; Group 3: low-dose antigen, high-dose adjuvant; and one placebo group (saline). Group 4 differed in that it received the vaccine three times, each one at days 0, 28, and 56, whereas all the other groups received the vaccine twice, once on day 0, and once on day 56. Within the vaccine groups, no SAEs were reported throughout the study duration.