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Citations to this article

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection
Philana Ling Lin, … , JoAnne L. Flynn, Peter Andersen
Philana Ling Lin, … , JoAnne L. Flynn, Peter Andersen
Published December 1, 2011
Citation Information: J Clin Invest. 2012;122(1):303-314. https://doi.org/10.1172/JCI46252.
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Research Article Immunology Article has an altmetric score of 7

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

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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.

Authors

Philana Ling Lin, Jes Dietrich, Esterlina Tan, Rodolfo M. Abalos, Jasmin Burgos, Carolyn Bigbee, Matthew Bigbee, Leslie Milk, Hannah P. Gideon, Mark Rodgers, Catherine Cochran, Kristi M. Guinn, David R. Sherman, Edwin Klein, Christopher Janssen, JoAnne L. Flynn, Peter Andersen

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2009 Total
Citations: 3 9 8 7 9 5 8 8 10 15 15 17 6 2 1 123
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2018 (8)

Title and authors Publication Year
Next-Generation Vaccines Based on Bacille Calmette–Guérin
NE Nieuwenhuizen, SH Kaufmann
Frontiers in immunology 2018
Formulation in DDA-MPLA-TDB Liposome Enhances the Immunogenicity and Protective Efficacy of a DNA Vaccine against Mycobacterium tuberculosis Infection
M Tian, Z Zhou, S Tan, X Fan, L Li, N Ullah
Frontiers in immunology 2018
Identification and Evaluation of Novel Protective Antigens for the Development of a Candidate TB Subunit Vaccine
E Stylianou, R Harrington-Kandt, J Beglov, N Bull, N Pinpathomrat, GM Swarbrick, DA Lewinsohn, DM Lewinsohn, H McShane
Infection and immunity 2018
Integrating Non-human Primate, Human, and Mathematical Studies to Determine the Influence of BCG Timing on H56 Vaccine Outcomes
LR Joslyn, E Pienaar, RM DiFazio, S Suliman, BM Kagina, JA Flynn, TJ Scriba, JJ Linderman, DE Kirschner
Frontiers in microbiology 2018
Nanoscale Peptide Self-assemblies Boost BCG-primed Cellular Immunity Against Mycobacterium tuberculosis
CB Chesson, M Huante, RJ Nusbaum, AG Walker, TM Clover, J Chinnaswamy, JJ Endsley, JS Rudra
Scientific Reports 2018
T Cells Primed by Live Mycobacteria Versus a Tuberculosis Subunit Vaccine Exhibit Distinct Functional Properties
T Lindenstrøm, A Moguche, M Damborg, EM Agger, K Urdahl, P Andersen
EBioMedicine 2018
Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques
AM Cadena, FF Hopkins, P Maiello, AF Carey, EA Wong, CJ Martin, HP Gideon, RM DiFazio, P Andersen, PL Lin, SM Fortune, JA Flynn, P Salgame
PLoS pathogens 2018
Dual-Isotope SPECT/CT Imaging of the Tuberculosis Subunit Vaccine H56/CAF01: Induction of Strong Systemic and Mucosal IgA and T-Cell Responses in Mice Upon Subcutaneous Prime and Intrapulmonary Boost Immunization
A Thakur, C Rodríguez-Rodríguez, K Saatchi, F Rose, T Esposito, Z Nosrati, P Andersen, D Christensen, UO Häfeli, C Foged
Frontiers in immunology 2018

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