title: A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates.
abstract: Bacille Calmette-Guérin (BCG) vaccination of new born babies can protect children against tuberculosis (TB), but fails to protect adults consistently against pulmonary TB underlying the urgent need to develop novel TB vaccines. Majority of first generation TB vaccine candidates have relied on a very limited number of antigens typically belonging to the active phase of infection. We have designed a multi-antigenic and multiphasic vaccine, based on the Modified Vaccinia Ankara virus (MVA). Up to fourteen antigens representative of the three phases of TB infection (active, latent and resuscitation) were inserted into MVA. Using three different strains of mouse (BALB/c, C57BL/6 and C3H/HeN), we show that a single vaccination results in induction of both CD4 and CD8 T cells, displaying capacity to produce multiple cytokines together with cytolytic activity targeting a large array of epitopes. As expected, dominance of responses was linked to the mouse haplotype although for a given haplotype, responses specific of at least one antigen per phase could always be detected. Vaccination of non-human primates with the 14 antigens MVA-TB candidate resulted in broad and potent cellular-based immunogenicity. The remarkable plasticity of MVA opens the road to development of a novel class of highly complex recombinant TB vaccines to be evaluated in both prophylactic and therapeutic settings.
authors.affiliation: Department of Infectious Diseases, Transgene, Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Leung-Theung-Long
authors.affiliation: Department of Infectious Diseases, Transgene, Lyon, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Gouanvic
authors.affiliation: Department of Infectious Diseases, Transgene, Lyon, France.
authors.forename: Charles-Antoine
authors.initials: CA
authors.lastname: Coupet
authors.affiliation: Department of Infectious Diseases, Transgene, Lyon, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ray
authors.affiliation: Department of Infectious Diseases, Transgene, Lyon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Tupin
authors.affiliation: Department of Smart Virus Lab, Transgene, Illkirch-Graffenstaden, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Silvestre
authors.affiliation: Department of Smart Virus Lab, Transgene, Illkirch-Graffenstaden, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Marchand
authors.affiliation: Department of Smart Virus Lab, Transgene, Illkirch-Graffenstaden, France.
authors.forename: Doris
authors.initials: D
authors.lastname: Schmitt
authors.affiliation: Department of Smart Virus Lab, Transgene, Illkirch-Graffenstaden, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Hoffmann
authors.affiliation: Department of Smart Virus Lab, Transgene, Illkirch-Graffenstaden, France.
authors.forename: Murielle
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Immunobiology, Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
authors.forename: Philip
authors.initials: P
authors.lastname: Seegren
authors.affiliation: Department of Immunobiology, Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Huaman
authors.affiliation: Department of Immunobiology, Advanced BioScience Laboratories, Inc., Rockville, Maryland, United States of America.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Cristillo
authors.affiliation: Department of Infectious Diseases, Transgene, Lyon, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Inchauspé
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009163:Mycobacterium bovis / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; C560489:MVA vaccine; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma