Editorial: Community series in research advances of tuberculosis vaccine and its implication on COVID-19, volume III

The relentless global burden of Tuberculosis (TB), causing over 10.7 million new cases and 1.25 million deaths in 2024, demands urgent innovation [1]. The limited and variable efficacy (0-80%) of the Bacille Calmette-Guérin (BCG) vaccine in adults, a challenge starkly highlighted during the COVID-19 pandemic, underscores the critical need for novel prophylactic and therapeutic strategies [2][3][4][5]. This third volume of our Research Topic, "Community Series in Research Advances of Tuberculosis Vaccine and its Implication on COVID-19," collates pioneering work that bridges immunology, nanotechnology, and clinical research. The eight articles herein not only provide deep insights into TB immunopathogenesis but also present tangible advances in vaccine design, diagnostic precision, and patient stratification, with broader implications for managing intracellular infections.This collection comprises eight articles (4 Research Articles, 2 Reviews, 2 Corrections) that collectively address critical bottlenecks in TB immunology, vaccine development and immunodiagnostics (Table 1). • Induced a strong DTH response in guinea pigs (induration of 18.3 ± 1.8 mm at 10μg/ml) with no cross-reactivity to BCG.• Preclinical assessment confirmed excellent safety and specificity, supporting its potential for clinical trials.Frontiers in Immunology • Identified a 3-gene cuproptosis-related signature (ASPHD2, GK, GCH1) for PTB diagnosis with high accuracy (AUCs: 0.981, 0.928, 0.937).• The signature was linked to a significantly altered immune microenvironment in PTB patients.• GCH1 and GK expression significantly decreased after one month of treatment (p<0.05),suggesting their utility as therapy monitoring biomarkers.Research Article Masoud Mortezazadeh et al.• LTBI prevalence was not significantly higher in cancer patients (27.1%) vs. controls (20.7%, P=0.176).• However, LTBI was a strong predictor of mortality in cancer patients (OR=3.28, P<0.001).• Each 1mm increase in TST induration was associated with a 6% increased risk of death (HR=1.06, P=0.001).5 Review Aishwarya Shaji et al.• Systematically reviewed the TB vaccine pipeline, noting the variable efficacy of BCG (0-80%).• Highlighted promising candidates like M72/AS01E, which showed 54% efficacy against MTB infection in adults.• Emphasized that host genetics (e.g., IFN-γ +874 T/A polymorphism) are a core determinant of vaccine efficacy, advocating for precision vaccinology. • Highlighted that MTB-specific IgM in BALF was the strongest correlate of reduced bacterial burden in primates.• Argued that future vaccines must be designed to elicit a precisely tuned humoral immune response. • Corrected errors in the labeling of figures in the supplementary materials.• Confirmed that the corrections do not affect any experimental data, statistical results, or the main conclusions of the study. • Restored the abstract to the authors' originally submitted version after a production error.• Clarified that the correction is textual only and does not alter any data or scientific conclusions presented in the article.The collective findings presented in this Research Topic create a powerful, synergistic narrative. They move the field forward not in isolated increments, but through a convergent evolution of ideas. However, the review by Huoming Li and Hao Li compellingly argues that this is an incomplete picture. The next frontier may lie in designing vaccines that not only elicit potent T-cell immunity but also guide the development of a protective antibody profile [8][9][10][11][12][13],perhaps using the very targeting technologies showcased in this topic. This integrated approach-orchestrating both arms of the adaptive immune system-is a cornerstone of modern vaccinology, as learned from COVID-19. The collective works in this Research Topic vividly illustrate a field in rapid and sophisticated evolution. From the nano-engineering of targeted immune stimulants and the computational discovery of diagnostic biomarkers, to the refined understanding of immune correlates and the translation of epidemiological data into clinical practice, this volume showcases a multi-faceted attack on TB. The integration of key quantitative findings-from vaccine efficacy rates and diagnostic AUC values to relative risk metricsprovides a solid evidence base for future research. These advances, particularly the lessons in leveraging innate immunity and understanding host-specific responses, resonate deeply with the broader vaccinology landscape, including the fight against COVID-19. As we move forward, the continued synergy between disruptive technology, basic immunology, and precision medicine will be paramount in achieving the ultimate goal: ending the TB epidemic.