ArticleThe Journal of clinical investigation2012
The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
131 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Vaccine against tuberculosis: what's new?BMC infectious diseases · 2014Pooled it
- A Phase I/II randomized trial of H56:IC31 vaccination and adjunctive cyclooxygenase-2-inhibitor treatment in tuberculosis patients.Nature communications · 2021Trial
- Intracellular Cytokine Staining and Flow Cytometry: Considerations for Application in Clinical Trials of Novel Tuberculosis Vaccines.PloS one · 2015Trial
- Trial
- Rv2656c: A Potential Candidate Antigen Associated with Latent Tuberculosis Infection.Vaccines · 2026Article
- An ESAT-6-convergent prime-boost vaccination combining recombinant BCG expressing Mycobacterium marinum ESX-1 and ESAT-6/GLA-SE improves TB protection.NPJ vaccines · 2026Article
- Immunotherapy targeting drug-tolerant Mycobacterium tuberculosis persisters accelerates tuberculosis cure in preclinical models.The Journal of clinical investigation · 2026Article
- Controlled human infection with Mycobacterium tuberculosis: practical considerations for clinical trials.The Lancet. Microbe · 2026Review
- Immunotherapy for tuberculosis: current strategies and future directions.Military Medical Research · 2025Review
- Article
- A vaccine targeting lung resident-memory CD4NPJ vaccines · 2025Article
- CD1-restricted T cells: are unconventional allies the key to future TB vaccines?Frontiers in immunology · 2025Review
- Heterologous prime-boost immunization combining parenteral and mucosal routes with different adjuvants mounts long-lived CD4+ T cell responses in lungs.Frontiers in immunology · 2025Article
- Relative Importance of Defined Mycobacterium tuberculosis Antigens in the T-Cell Recognition Repertoire of Latently Infected Individuals Not Progressing to Active Disease.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Article
- Model systems to studyFrontiers in cellular and infection microbiology · 2025Review
- A multistage Sendai virus vaccine incorporating latency-associated antigens induces protection against acute and latent tuberculosis.Emerging microbes & infections · 2024Article
- An intranasal nanoparticle vaccine elicits protective immunity against Mycobacterium tuberculosis.Vaccine · 2024Article
- Review
- The BCG vaccine, advantages, and disadvantages of introducing new generation vaccines againstClinical and experimental vaccine research · 2024Review
- Optimizing antigen selection for the development of tuberculosis vaccines.Cell insight · 2024Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
It is estimated that one-third of the world's population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress-induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.