No abstract

Mycobacterium tuberculosis complex causes tuberculosis (TB), one of the top 10 causes of death worldwide. TB results in more fatalities than multi-drug resistant (MDR) HIV strain related coinfection. Vaccines play a key role in the prevention and control of infectious diseases. Unfortunately, the only licensed preventive vaccine against TB, bacilli Calmette-Guérin (BCG), is ineffective for prevention of pulmonary TB in adults. Therefore, it is very important to develop novel vaccines for TB prevention and control. This literature review provides an overview of the innate and adaptive immune response during M. tuberculosis infection, and presents current developments and challenges to novel TB vaccines. A comprehensive understanding of vaccines in preclinical and clinical studies provides extensive insight for the development of safer and more efficient vaccines, and may inspire new ideas for TB prevention and treatment.

As an ancient infectious disease, tuberculosis (TB) is still the leading cause of death from a single infectious agent worldwide. Latent TB infection (LTBI) has been recognized as the largest source of new TB cases and is one of the biggest obstacles to achieving the aim of the End TB Strategy. The latest data indicate that a considerable percentage of the population with LTBI and the lack of differential diagnosis between LTBI and active TB (aTB) may be potential reasons for the high TB morbidity and mortality in countries with high TB burdens. The tuberculin skin test (TST) has been used to diagnose TB for > 100 years, but it fails to distinguish patients with LTBI from those with aTB and people who have received Bacillus Calmette–Guérin vaccination. To overcome the limitations of TST, several new skin tests and interferon-gamma release assays have been developed, such as the Diaskintest, C-Tb skin test, EC-Test, and T-cell spot of the TB assay, QuantiFERON-TB Gold In-Tube, QuantiFERON-TB Gold-Plus, LIAISON QuantiFERON-TB Gold Plus test, and LIOFeron TB/LTBI. However, these methods cannot distinguish LTBI from aTB. To investigate the reasons why all these methods cannot distinguish LTBI from aTB, we have explained the concept and definition of LTBI and expounded on the immunological mechanism of LTBI in this review. In addition, we have outlined the research status, future directions, and challenges of LTBI differential diagnosis, including novel biomarkers derived from Mycobacterium tuberculosis and hosts, new models and algorithms, omics technologies, and microbiota.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. As a result of the coronavirus disease 2019 (COVID-19) pandemic, the global TB mortality rate in 2020 is rising, making TB prevention and control more challenging. Vaccination has been considered the best approach to reduce the TB burden. Unfortunately, BCG, the only TB vaccine currently approved for use, offers some protection against childhood TB but is less effective in adults. Therefore, it is urgent to develop new TB vaccines that are more effective than BCG. Accumulating data indicated that peptides or epitopes play essential roles in bridging innate and adaptive immunity and triggering adaptive immunity. Furthermore, innovations in bioinformatics, immunoinformatics, synthetic technologies, new materials, and transgenic animal models have put wings on the research of peptide-based vaccines for TB. Hence, this review seeks to give an overview of current tools that can be used to design a peptide-based vaccine, the research status of peptide-based vaccines for TB, protein-based bacterial vaccine delivery systems, and animal models for the peptide-based vaccines. These explorations will provide approaches and strategies for developing safer and more effective peptide-based vaccines and contribute to achieving the WHO’s End TB Strategy.

BackgroundTuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines.MethodsIn this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT.ResultsSix immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ+ T lymphocytes, CD3+IFN-γ+ T lymphocytes, and the MP3RT-specific IgG antibody.ConclusionsTaken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3+IFN-γ+ T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.