Evaluating the immunogenicity and safety of ID93 + GLA-SE in BCG-vaccinated healthy adults: a systematic review and meta-analysis of randomized controlled trials.

Abstract

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is an ancient disease that continues to pose a significant threat to global public health. Although the BCG vaccine, developed in the 1920s, remains the only approved TB vaccine, it has limited efficacy, particularly against pulmonary TB in adults. The ID93/GLA-SE vaccine, a recombinant subunit vaccine, shows promise by triggering immune solid responses and could be a key solution in combating TB, particularly in the face of rising drug-resistant strains and suboptimal current vaccines. It has the potential to address the unmet need for more effective interventions against drug-resistant TB, a growing global health issue that continues to challenge existing treatment options.

Objective: To evaluate the immunogenicity and safety of ID93 + GLA-SE in BCG-vaccinated healthy adults.

Methods: A comprehensive electronic search on PubMed (Medline), ScienceDirect, EMBASE, Scopus, and Cochrane Central database was conducted from inception till August 2024 for randomized controlled trials (RCTs) with a target population of BCG-vaccinated healthy adults. This review was conducted according to (PRISMA) criteria and registered with PROSPERO (CRD42024601450). This meta-analysis used Review Manager and forest plots for visual display. The outcomes were displayed as risk ratios (RR) with a 95% confidence interval.

Results: The ID93 + GLA-SE vaccine showed strong immunogenicity, particularly in high doses, with robust IgG responses sustained up to day 421 in all studies, significantly higher than baseline, and seroconversion rates remained high through day 84. CD4 T-cell responses peaked after the third dose and remained elevated through day 421, whereas CD8 T-cell responses were minimal. Regarding adverse effects, the ID93 + GLA-SE vaccine significantly increases fatigue (RR 3.24, p = 0.005), myalgia (RR 5.82, p < 0.0001), and injection site pain (RR 4.12, p < 0.00001), compared to placebo, with consistent results across both high and low doses. However, there were no significant differences for upper respiratory tract infections, 0.83 (95% CI 0.38-1.84, p = 0.87) or 1.77 (95% CI 0.77-4.10, p = 0.18) headaches. Dose optimization remains crucial due to the higher side effect risks of increased doses.

Conclusion: The ID93 + GLA-SE vaccine shows a solid safety profile and enhances immune responses, especially IgG and CD4+ T-cell activity, which is crucial for TB defense. Higher doses improve efficacy but increase side effects, highlighting the need for dose optimization. As a potential alternative to the BCG vaccine, especially in drug-resistant TB regions, further research should refine dosage and assess long-term safety.