A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis

Stéphane Leung-Theung-Long, Charles Antoine Coupet, Marie Gouanvic, Doris Schmitt, Aurélie Ray, Chantal Hoffmann, Huguette Schultz, Sandeep Tyagi, Heena Soni, Paul J. Converse, Lilibeth Arias, Patricia Kleinpeter, Benoît Sansas, Khisimuzi Mdluli, Cristina Vilaplana, Pere Joan Cardona, Eric Nuermberger, Jean Baptiste Marchand, Nathalie Silvestre, Geneviève Inchauspé

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Abstract

© 2018 Leung-Theung-Long et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Despite the existence of the prophylactic Bacille Calmette-Guérin (BCG) vaccine, infection by Mycobacterium tuberculosis (Mtb) remains a major public health issue causing up to 1.8 million annual deaths worldwide. Increasing prevalence of Mtb strains resistant to antibiotics represents an urgent threat for global health that has prompted a search for alternative treatment regimens not subject to development of resistance. Immunotherapy constitutes a promising approach to improving current antibiotic treatments through engagement of the host’s immune system. We designed a multi-antigenic and multiphasic vaccine, based on the Modified Vaccinia Ankara (MVA) virus, denoted MVATG18598, which expresses ten antigens classically described as representative of each of different phases of Mtb infection. In vitro analysis coupled with multiple-passage evaluation demonstrated that this vaccine is genetically stable, i.e. fit for manufacturing. Using different mouse strains, we show that MVATG18598 vaccination results in both Th1-associated T-cell responses and cytolytic activity, targeting all 10 vaccine-expressed Mtb antigens. In chronic post-exposure mouse models, MVATG18598 vaccination in combination with an antibiotic regimen decreases the bacterial burden in the lungs of infected mice, compared with chemotherapy alone, and is associated with long-lasting antigen-specific Th1-type T cell and antibody responses. In one model, co-treatment with MVATG18598 prevented relapse of the disease after treatment completion, an important clinical goal. Overall, results demonstrate the capacity of the therapeutic MVATG18598 vaccine to improve efficacy of chemotherapy against TB. These data support further development of this novel immunotherapeutic in the treatment of Mtb infections.
Original languageEnglish
Article numbere0196815
JournalPLoS ONE
Volume13
Issue number5
DOIs
Publication statusPublished - 1 May 2018

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    Leung-Theung-Long, S., Coupet, C. A., Gouanvic, M., Schmitt, D., Ray, A., Hoffmann, C., Schultz, H., Tyagi, S., Soni, H., Converse, P. J., Arias, L., Kleinpeter, P., Sansas, B., Mdluli, K., Vilaplana, C., Cardona, P. J., Nuermberger, E., Marchand, J. B., Silvestre, N., & Inchauspé, G. (2018). A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis. PLoS ONE, 13(5), [e0196815]. https://doi.org/10.1371/journal.pone.0196815