About this Research Topic
Tuberculosis (TB) remains a major global health problem, with over a million deaths annually. Effective TB vaccines and shorter treatment regimens are needed to end the global TB epidemic. A new TB vaccine with greater protective efficacy than the Bacille Calmette-Guérin (BCG) vaccine that can prevent disease in adolescents and adults is essential for global TB elimination. With current pathogen-targeting antibiotic-based strategies, progress toward eliminating TB is inadequate, and new ideas to enhance immune resistance using improved vaccination, novel therapies, or combination approaches are necessary. Host-directed therapies have received increased attention recently as a potential treatment strategy for TB through therapeutic augmentation of protective immunity and minimizing the long-term tissue-damaging effects of infection and antibiotic treatment. Such immunotherapies can also be helpful in the treatment of TB co-infections and co-morbidities, such as HIV, SARS-CoV-2 infections, and type II diabetes. Multiple host-directed molecular therapeutics are currently being evaluated in clinical trials as an adjunct to antibiotic therapy. A renewed promise of an effective vaccine has also emerged lately, and several TB vaccine candidates are in phase-2b and phase-3 trials, and efficacy data are anticipated soon.
However, despite the evolution of vaccine candidates, platforms, and host-directed therapeutics over the last two decades, none are expected to be a ‘magic bullet’ or ‘wonder drug.’ The challenges posed by the incomplete understanding of protective antigens, host-pathogen interactions, and bacterial elimination at the granuloma levels are the major impediments to the progress. Very few new vaccine candidates are currently in phase-1 clinical trials, and identification of new candidates is needed to ensure that the vaccine pipeline remains robust. The quest for immune correlates of vaccine-mediated protection and identification of host pathways that molecular therapeutics can safely target to eliminate mycobacteria in granulomas are necessary. The role of infection spectrum and granuloma heterogeneity in vaccine and host-directed treatment outcomes needs a better understanding. New tools and high-dimensional omics-based technologies to discover effective immunotherapeutics and evaluate the potential vaccine efficacy will be required to advance the field of prophylactic or therapeutic vaccination and small molecule therapies for TB.
In this Research Topic, we welcome the submission of Original Research, Brief Research Reports, Methods, state-of-the-art Reviews, Perspectives, and Mini-Reviews that present technological and conceptual advances and challenge dogma in all fundamental and translational aspects of vaccines and molecular therapeutics against TB, associated co-infections, and co-morbidities.
We welcome submissions in the following areas:
• Vaccination and host-directed therapeutic approaches for preventing infection and disease progression, treating disease, preventing relapse, and shortening treatment against TB and associated co-infections and co-morbidities.
• Combination vaccine and molecular therapeutic approaches for drug-susceptible and resistant TB.
• Development of new tools to discover and characterize the efficacy of vaccine candidates and molecular therapeutics.
• Recombinant subunit, live attenuated, synthetic peptide, viral vector, polyprotein mRNA, nanotechnology-based, needle-free, and other vaccine approaches.
• Small molecular therapeutics, their immune pathway targets, and individual or adjunctive efficacy in vitro and in vivo.
• Elucidation of immune mechanisms, immunological readouts, and immune correlates of protection.
• Vaccine engineering, small molecular discovery, regimen design, and delivery.
• Small molecules and host-directed therapeutics as TB vaccine adjuvants.
• Preclinical animal models of infection, disease, and transmission prevention.
• Understanding granuloma heterogeneity and microenvironments and the impact on vaccine and host-directed therapeutic efficacy.
• Vaccine, molecular therapeutic-induced innate and acquired immunity, trained immunity, immune tolerance, and immune amnesia against TB.
However, despite the evolution of vaccine candidates, platforms, and host-directed therapeutics over the last two decades, none are expected to be a ‘magic bullet’ or ‘wonder drug.’ The challenges posed by the incomplete understanding of protective antigens, host-pathogen interactions, and bacterial elimination at the granuloma levels are the major impediments to the progress. Very few new vaccine candidates are currently in phase-1 clinical trials, and identification of new candidates is needed to ensure that the vaccine pipeline remains robust. The quest for immune correlates of vaccine-mediated protection and identification of host pathways that molecular therapeutics can safely target to eliminate mycobacteria in granulomas are necessary. The role of infection spectrum and granuloma heterogeneity in vaccine and host-directed treatment outcomes needs a better understanding. New tools and high-dimensional omics-based technologies to discover effective immunotherapeutics and evaluate the potential vaccine efficacy will be required to advance the field of prophylactic or therapeutic vaccination and small molecule therapies for TB.
In this Research Topic, we welcome the submission of Original Research, Brief Research Reports, Methods, state-of-the-art Reviews, Perspectives, and Mini-Reviews that present technological and conceptual advances and challenge dogma in all fundamental and translational aspects of vaccines and molecular therapeutics against TB, associated co-infections, and co-morbidities.
We welcome submissions in the following areas:
• Vaccination and host-directed therapeutic approaches for preventing infection and disease progression, treating disease, preventing relapse, and shortening treatment against TB and associated co-infections and co-morbidities.
• Combination vaccine and molecular therapeutic approaches for drug-susceptible and resistant TB.
• Development of new tools to discover and characterize the efficacy of vaccine candidates and molecular therapeutics.
• Recombinant subunit, live attenuated, synthetic peptide, viral vector, polyprotein mRNA, nanotechnology-based, needle-free, and other vaccine approaches.
• Small molecular therapeutics, their immune pathway targets, and individual or adjunctive efficacy in vitro and in vivo.
• Elucidation of immune mechanisms, immunological readouts, and immune correlates of protection.
• Vaccine engineering, small molecular discovery, regimen design, and delivery.
• Small molecules and host-directed therapeutics as TB vaccine adjuvants.
• Preclinical animal models of infection, disease, and transmission prevention.
• Understanding granuloma heterogeneity and microenvironments and the impact on vaccine and host-directed therapeutic efficacy.
• Vaccine, molecular therapeutic-induced innate and acquired immunity, trained immunity, immune tolerance, and immune amnesia against TB.
Keywords: Tuberculosis, TB, HIV, HIV co-infection, vaccine, molecular therapeutics, host-directed therapy, immunotherapy, BCG, animal models
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
