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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: 1 8 8 7 9 5 8 8 10 15 15 17 6 2 1 120
Citation information
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Citations to this article in year 2015 (15)

Title and authors Publication Year
The DosR Regulon Modulates Adaptive Immunity and is Essential for M. tuberculosis Persistence
S Mehra, TW Foreman, PJ Didier, MH Ahsan, TA Hudock, R Kissee, NA Golden, US Gautam, AM Johnson, X Alvarez, KE Russell-Lodrigue, LA Doyle, CJ Roy, JL Blanchard, SA Khader, AA Lackner, DR Sherman, D Kaushal
American journal of respiratory and critical care medicine 2015
Vaccines for TB: Lessons from the Past Translating into Future Potentials
GJ Tye, MH Lew, YS Choong, TS Lim, ME Sarmiento, A Acosta, MN Norazmi
Journal of Immunology Research 2015
Intracellular Cytokine Staining and Flow Cytometry: Considerations for Application in Clinical Trials of Novel Tuberculosis Vaccines
SG Smith, K Smits, SA Joosten, KE van Meijgaarden, I Satti, HA Fletcher, N Caccamo, F Dieli, F Mascart, H McShane, HM Dockrell, TH Ottenhoff, TJ Scriba
PloS one 2015
Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis
D Kaushal, TW Foreman, US Gautam, X Alvarez, T Adekambi, J Rangel-Moreno, NA Golden, AM Johnson, BL Phillips, MH Ahsan, KE Russell-Lodrigue, LA Doyle, CJ Roy, PJ Didier, JL Blanchard, J Rengarajan, AA Lackner, SA Khader, S Mehra
Nature Communications 2015
Tuberculosis vaccines: barriers and prospects on the quest for a transformative tool
CL Karp, CB Wilson, LM Stuart
Immunological Reviews 2015
Immunology studies in non-human primate models of tuberculosis
JA Flynn, HP Gideon, JT Mattila, PL Lin
Immunological Reviews 2015
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
X Wang, J Zhang, J Liang, Y Zhang, X Teng, X Yuan, X Fan, MM Rodrigues
PloS one 2015
Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection
T Hoang, EM Agger, JP Cassidy, JP Christensen, P Andersen, S Ehrt
Infection and immunity 2015
A multi-scale approach to designing therapeutics for tuberculosis
JJ Linderman, NA Cilfone, E Pienaar, C Gong, DE Kirschner
Integrative Biology 2015
Recent advances in the development of vaccines for tuberculosis
MJ Ahsan
Therapeutic advances in vaccines 2015
Synthetic Long Peptide Derived from Mycobacterium tuberculosis Latency Antigen Rv1733c Protects against Tuberculosis
M Coppola, SJ van Eeden, L Wilson, KL Franken, TH Ottenhoff, A Geluk, DW Pascual
Clinical and vaccine immunology : CVI 2015
A high ratio of IC31 ® adjuvant to antigen is necessary for H4 TB vaccine immunomodulation
S Aboutorabian, J Hakimi, F Boudet, S Montano, A Dookie, C Roque, SF Ausar, N Rahman, RH Brookes
Human Vaccines & Immunotherapeutics 2015
Transformative tools for tackling tuberculosis
JL Gardiner, CL Karp
Journal of Experimental Medicine 2015
Evaluation of Humoral Immunity to Mycobacterium tuberculosis -Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development
M Niki, M Suzukawa, S Akashi, H Nagai, K Ohta, M Inoue, M Niki, Y Kaneko, K Morimoto, A Kurashima, S Kitada, S Matsumoto, K Suzuki, Y Hoshino
Journal of Immunology Research 2015
A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates
S Leung-Theung-Long, M Gouanvic, CA Coupet, A Ray, E Tupin, N Silvestre, JB Marchand, D Schmitt, C Hoffmann, M Klein, P Seegren, MC Huaman, AD Cristillo, G Inchauspé, AA Izzo
PloS one 2015

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