A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates.
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4658014?pdf=render |
| _version_ | 1819157342960222208 |
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| author | Stéphane Leung-Theung-Long Marie Gouanvic Charles-Antoine Coupet Aurélie Ray Emmanuel Tupin Nathalie Silvestre Jean-Baptiste Marchand Doris Schmitt Chantal Hoffmann Murielle Klein Philip Seegren Maria C Huaman Anthony D Cristillo Geneviève Inchauspé |
| author_facet | Stéphane Leung-Theung-Long Marie Gouanvic Charles-Antoine Coupet Aurélie Ray Emmanuel Tupin Nathalie Silvestre Jean-Baptiste Marchand Doris Schmitt Chantal Hoffmann Murielle Klein Philip Seegren Maria C Huaman Anthony D Cristillo Geneviève Inchauspé |
| author_sort | Stéphane Leung-Theung-Long |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T16:07:15Z |
| format | Article |
| id | doaj.art-90e56612c9964e54a8a4696ebc738c29 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T16:07:15Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-90e56612c9964e54a8a4696ebc738c292022-12-21T18:20:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e014355210.1371/journal.pone.0143552A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates.Stéphane Leung-Theung-LongMarie GouanvicCharles-Antoine CoupetAurélie RayEmmanuel TupinNathalie SilvestreJean-Baptiste MarchandDoris SchmittChantal HoffmannMurielle KleinPhilip SeegrenMaria C HuamanAnthony D CristilloGeneviève InchauspéBacille 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.http://europepmc.org/articles/PMC4658014?pdf=render |
| spellingShingle | Stéphane Leung-Theung-Long Marie Gouanvic Charles-Antoine Coupet Aurélie Ray Emmanuel Tupin Nathalie Silvestre Jean-Baptiste Marchand Doris Schmitt Chantal Hoffmann Murielle Klein Philip Seegren Maria C Huaman Anthony D Cristillo Geneviève Inchauspé A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates. PLoS ONE |
| title | A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates. |
| title_full | A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates. |
| title_fullStr | A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates. |
| title_full_unstemmed | A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates. |
| title_short | A Novel MVA-Based Multiphasic Vaccine for Prevention or Treatment of Tuberculosis Induces Broad and Multifunctional Cell-Mediated Immunity in Mice and Primates. |
| title_sort | novel mva based multiphasic vaccine for prevention or treatment of tuberculosis induces broad and multifunctional cell mediated immunity in mice and primates |
| url | http://europepmc.org/articles/PMC4658014?pdf=render |
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