Community Series in research advances of Tuberculosis vaccine and its implication on COVID-19: volume IV

Tuberculosis (TB), caused by Mycobacterium tuberculosis complex, remains a leading cause of death from a single infectious agent worldwide. Vaccination is a cornerstone of TB prevention and control. However, the only currently licensed vaccine, Bacille Calmette-Guérin (BCG), exhibits highly variable efficacy (0–80%) in adults and provides limited protection lasting only 10–15 years. Consequently, the development of novel, more effective TB vaccines is an urgent global priority.According to the Global Tuberculosis Report 2025 released by the World Health Organization (WHO), more than a dozen TB vaccine candidates are now in various phases of clinical trials. Despite this progress, significant challenges persist, including an incomplete understanding of M. tuberculosis pathogenesis, the delicate immune balance between bacterial virulence and host defense, and suboptimal protective efficacy in clinical trials. Moreover, the heterogeneity of human immune responses to TB infection calls for better preclinical models and robust correlates of protection.Importantly, although the acute phase of the COVID-19 pandemic has subsided, SARS-CoV-2 continues to circulate, and the long-term consequences of the pandemic – including post-COVID conditions (“long COVID”), immune dysregulation, and disrupted healthcare systems – continue to impact TB control efforts. Co-infection with TB and SARS-CoV-2 has been shown to exacerbate clinical outcomes and increase mortality. On the other hand, growing evidence suggests that BCG-induced “trained immunity” – a functional reprogramming of innate immune cells – may offer non-specific protection against respiratory infections, including SARS-CoV-2. However, the molecular mechanisms underlying trained immunity, its durability, and its potential to mitigate COVID-19 severity or co-infections remain to be fully elucidated. Furthermore, lessons learned from the rapid development of COVID-19 vaccines (e.g., mRNA platforms, viral-vectored vaccines) can be leveraged to accelerate TB vaccine research.This Research Topic, the fourth volume of the “Community Series in Research Advances of Tuberculosis Vaccine and its Implication on COVID-19”, aims to provide a comprehensive overview of innate and adaptive immune responses to M. tuberculosis infection, innovative technologies for vaccine design and evaluation, and recent advances in TB vaccine development – with an expanded focus on cross-cutting themes relevant to COVID-19 and other respiratory pathogens. We welcome Original Research, Clinical Trials, Mini-reviews, Reviews, Systematic Reviews, Perspectives, and Data Reports related to the following subtopics (including but not limited to):Novel insights into immune mechanisms of M. tuberculosis infection, including host protective immunity (e.g., tissue-resident memory T cells, B cell responses, trained immunity), immune evasion strategies, and immunometabolism.Trained immunity induced by BCG and other vaccines: molecular and epigenetic mechanisms, duration of protection, and clinical/epidemiological evidence for cross-protection against COVID-19, other respiratory viruses, and co-infections.Immunotherapeutic vaccines and BCG revaccination: protective immune responses induced in different populations (e.g., adolescents, adults, elderly, people living with HIV), and their potential to reduce TB disease burden.Emerging TB vaccine candidates in preclinical and clinical studies, particularly those leveraging next-generation platforms such as mRNA, self-amplifying RNA, viral vectors (e.g., adenovirus, MVA), virus-like particles (VLPs), and nanoparticle-based delivery systems.Application of bioinformatics, immunoinformatics, structural vaccinology, and artificial intelligence (AI) in the rational design of novel TB antigens, epitope prediction, vaccine construction, and optimization of multivalent or universal vaccines.In silico, in vitro, and in vivo comparative studies evaluating antigenicity, toxicity, allergenicity, immunogenicity, and protective efficacy of TB vaccines, including high-throughput screening methods and machine learning-based modeling.Advanced animal models and human challenge models that more accurately recapitulate the heterogeneity of human immune responses to M. tuberculosis, including non-human primates, humanized mice, and models of latent TB, reactivation, and co-morbidities (e.g., diabetes, HIV, COVID-19).Vaccine formulation and immunization strategies: novel adjuvants (e.g., TLR agonists, saponin-based adjuvants), optimized routes (intradermal, mucosal, aerosol), dosing regimens, and heterologous prime-boost approaches to enhance potency and durability.Impact of the COVID-19 pandemic on TB vaccination programs and clinical trials, including disruptions to BCG coverage, vaccine hesitancy, repurposing of TB vaccine candidates for COVID-19, and lessons for future pandemic preparedness.Host-pathogen-immune interactions in TB-COVID-19 co-infection: immunological signatures, immunopathology, biomarkers of disease progression or protection, and therapeutic or prophylactic strategies addressing both diseases.Biomarkers and correlates of protection for TB vaccines – leveraging omics technologies (transcriptomics, proteomics, metabolomics) and systems vaccinology approaches to predict vaccine efficacy in humans.Global health, equity, and implementation research – barriers and facilitators for rolling out novel TB vaccines in high-burden settings, cost-effectiveness modeling, and strategies to integrate TB and COVID-19 vaccination campaigns.By expanding the scope to encompass cross-protection, co-infection, advanced technologies, and real-world implementation, this Research Topic aims to catalyze interdisciplinary collaboration and accelerate the development of next-generation TB vaccines that are effective not only against TB but also potentially against future respiratory pandemics. We cordially invite researchers from vaccinology, immunology, infectious diseases, computational biology, and public health to contribute their latest findings to this exciting collection.---Dr. Leite founded the start-up working on the development of TB vaccines: BCGene. Additionally, she is an employee of Instituto Butantan, owner of a patent on TB vaccines, of which she is an inventor. Topic editors: Luciana C C Leite, Wenping Gong, Hao Li Source: https://www.frontiersin.org/research-topics/80397/community-series-in-research-advances-of-tuberculosis-vaccine-and-its-implication-on-covid-19-volume-iv