ArticlePloS one2015
Protection against Mycobacterium tuberculosis infection offered by a new multistage subunit vaccine correlates with increased number of IFN-γ+ IL-2+ CD4+ and IFN-γ+ CD8+ T cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Tuberculosis vaccines and therapeutic drug: challenges and future directions.Molecular biomedicine · 2025Review
- Testing the Antigenic Potential of Transmembrane Proteins To Develop a Thermostable Tuberculosis MOF-Liposomal Vaccine.ACS infectious diseases · 2025Article
- Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhancesFrontiers in immunology · 2025Article
- Enhanced Immune Responses AgainstIndian journal of microbiology · 2024Article
- Review
- The role of the immune response in developing tuberculosis infection: from latent infection to active tuberculosis.Frontiers in tuberculosis · 2024Review
- Enhancement of the immunogenicity of aIranian journal of basic medical sciences · 2024Article
- A whole blood intracellular cytokine assay optimised for field site studies demonstrates polyfunctionality of CD4+ T cells in acute scrub typhus.PLoS neglected tropical diseases · 2023Article
- Protective RNA nanovaccines againstFrontiers in immunology · 2023Article
- Evaluating the Performance of PPE44, HSPX, ESAT-6 and CFP-10 Factors in Tuberculosis Subunit Vaccines.Current microbiology · 2022Review
- Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses AgainstFrontiers in cellular and infection microbiology · 2022Article
- Photochemically-Mediated Inflammation and Cross-Presentation ofFrontiers in immunology · 2022Article
- Comparison of Lethal and Nonlethal Mouse Models ofTropical medicine and infectious disease · 2021Article
- Preclinical Progress of Subunit and Live AttenuatedPharmaceutics · 2020Review
- Heterologous Boosting WithFrontiers in immunology · 2020Article
- A single dose polyanhydride-based nanovaccine against paratuberculosis infection.NPJ vaccines · 2020Article
- Differential Immunogenicity and Protective Efficacy Elicited by MTO- and DMT-Adjuvanted CMFO Subunit Vaccines againstJournal of immunology research · 2020Article
- Combinational PRR Agonists in Liposomal Adjuvant Enhances Immunogenicity and Protective Efficacy in a Tuberculosis Subunit Vaccine.Frontiers in immunology · 2020Article
- M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.Scientific reports · 2019Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein subunit vaccines present a compelling new area of research for control of tuberculosis (TB). Based on the interaction between Mycobacterium tuberculosis and its host, five stage-specific antigens of M. tuberculosis that participate in TB pathogenesis--Rv1813, Rv2660c, Ag85B, Rv2623, and HspX--were selected. These antigens were verified to be recognized by T cells from a total of 42 whole blood samples obtained from active TB patients, patients with latent TB infections (LTBIs), and healthy control donors. The multistage polyprotein A1D4 was developed using the selected five antigens as a potentially more effective novel subunit vaccine. The immunogenicity and protective efficacy of A1D4 emulsified in the adjuvant MTO [monophosphoryl lipid A (MPL), trehalose-6,6'-dibehenate (TDB), components of MF59] was compared with Bacillus Calmette-Guerin (BCG) in C57BL/6 mice. Our results demonstrated that A1D4/MTO could provide more significant protection against M. tuberculosis infection than the PBS control or MTO adjuvant alone judging from the A1D4-specific Th1-type immune response; however, its efficacy was inferior to BCG as demonstrated by the bacterial load in the lung and spleen, and by the pathological changes in the lung. Antigen-specific single IL-2-secreting cells and different combinations with IL-2-secreting CD4+ T cells were beneficial and correlated with BCG vaccine-induced protection against TB. Antigen-specific IFN-γ+ IL-2+ CD4+ T cells were the only effective biomarker significantly induced by A1D4/MTO. Among all groups, A1D4/MTO immunization also conferred the highest number of antigen-specific single IFN-γ+ and IFN-γ+ TNF-α+ CD4+ T cells, which might be related to the antigen load in vivo, and single IFN-γ+ CD8+ T cells by mimicking the immune patterns of LTBIs or curable TB patients. Our strategy seems promising for the development of a TB vaccine based on multistage antigens, and subunit antigen A1D4 suspended in MTO adjuvant warrants preclinical evaluation in animal models of latent infection and may boost BCG vaccination.
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