A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis
Infectious Diseases department, Centre d'Infectiologie, Bât Domilyon, Lyon
Coupet, Charles-Antoine (Infectious Diseases department, Centre d'Infectiologie, Bât Domilyon, Lyon)
Gouanvic, Marie (Infectious Diseases department, Centre d'Infectiologie, Bât Domilyon, Lyon)
Schmitt, Doris (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Ray, Aurélie (Infectious Diseases department, Centre d'Infectiologie, Bât Domilyon, Lyon)
Hoffmann, Chantal (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Schultz, Huguette (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Tyagi, Sandeep (Johns Hopkins University, Baltimore)
Soni, Heena (Johns Hopkins University, Baltimore)
Converse, Paul J. (Johns Hopkins University, Baltimore)
Arias, Lilibeth (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Kleinpeter, Patricia (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Sansas, Benoît (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Mdluli, Khisimuzi (Global Alliance for Tuberculosis Drug Development, New York)
Vilaplana, Cristina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Cardona, Pere-Joan (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Nuermberger, Eric (Johns Hopkins University, Baltimore, Maryland)
Marchand, Jean-Baptiste (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Silvestre, Nathalie (Boulevard Gonthier d'Andernach, Parc d'innovation, Illkirch-Graffenstaden)
Inchauspé, Geneviève (Infectious Diseases department, Centre d'Infectiologie, Bât Domilyon, Lyon)

Date:	2018
Abstract:	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.
Grants:	European Commission. Horizon 2020 CB06/05/0042
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 13 (may 2018) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0196815
PMID: 29718990

26 p, 5.0 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles