Prevention of tuberculosis in macaques after intravenous BCG immunization
Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we sho...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2020
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| Online Access: | https://hdl.handle.net/1721.1/128216 |
| _version_ | 1826194190909833216 |
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| author | Darrah, Patricia A. Zeppa, Joseph J. Maiello, Pauline Hackney, Joshua A. Wadsworth, Marc Havens Hughes, Travis K. Pokkali, Supriya Swanson II, Phillip A. Grant, Nicole L. Rodgers, Mark A. Kamath, Megha Causgrove, Chelsea M. Laddy, Dominick J. Bonavia, Aurelio Casimiro, Danilo Lin, Philana Ling Klein, Edwin White, Alexander G. Scanga, Charles A. Shalek, Alexander K Roederer, Mario Flynn, JoAnne L. Seder, Robert A. |
| author2 | Massachusetts Institute of Technology. Department of Chemistry |
| author_facet | Massachusetts Institute of Technology. Department of Chemistry Darrah, Patricia A. Zeppa, Joseph J. Maiello, Pauline Hackney, Joshua A. Wadsworth, Marc Havens Hughes, Travis K. Pokkali, Supriya Swanson II, Phillip A. Grant, Nicole L. Rodgers, Mark A. Kamath, Megha Causgrove, Chelsea M. Laddy, Dominick J. Bonavia, Aurelio Casimiro, Danilo Lin, Philana Ling Klein, Edwin White, Alexander G. Scanga, Charles A. Shalek, Alexander K Roederer, Mario Flynn, JoAnne L. Seder, Robert A. |
| author_sort | Darrah, Patricia A. |
| collection | MIT |
| description | Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis. |
| first_indexed | 2024-09-23T09:52:20Z |
| format | Article |
| id | mit-1721.1/128216 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:52:20Z |
| publishDate | 2020 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1282162022-09-30T17:22:34Z Prevention of tuberculosis in macaques after intravenous BCG immunization Darrah, Patricia A. Zeppa, Joseph J. Maiello, Pauline Hackney, Joshua A. Wadsworth, Marc Havens Hughes, Travis K. Pokkali, Supriya Swanson II, Phillip A. Grant, Nicole L. Rodgers, Mark A. Kamath, Megha Causgrove, Chelsea M. Laddy, Dominick J. Bonavia, Aurelio Casimiro, Danilo Lin, Philana Ling Klein, Edwin White, Alexander G. Scanga, Charles A. Shalek, Alexander K Roederer, Mario Flynn, JoAnne L. Seder, Robert A. Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Institute for Medical Engineering & Science Koch Institute for Integrative Cancer Research at MIT Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide1. The only available vaccine, BCG (Bacillus Calmette–Guérin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission1,2. Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography–computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis. 2020-10-27T19:46:57Z 2020-10-27T19:46:57Z 2020-01 2019-06 2020-09-22T15:50:05Z Article http://purl.org/eprint/type/JournalArticle 1476-4687 https://hdl.handle.net/1721.1/128216 Darrah, Patricia A. et al. "Prevention of tuberculosis in macaques after intravenous BCG immunization." Nature 577, 7788 (January 2020): 95–102 © 2020 The Author(s) en http://dx.doi.org/10.1038/S41586-019-1817-8 Nature Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature |
| spellingShingle | Darrah, Patricia A. Zeppa, Joseph J. Maiello, Pauline Hackney, Joshua A. Wadsworth, Marc Havens Hughes, Travis K. Pokkali, Supriya Swanson II, Phillip A. Grant, Nicole L. Rodgers, Mark A. Kamath, Megha Causgrove, Chelsea M. Laddy, Dominick J. Bonavia, Aurelio Casimiro, Danilo Lin, Philana Ling Klein, Edwin White, Alexander G. Scanga, Charles A. Shalek, Alexander K Roederer, Mario Flynn, JoAnne L. Seder, Robert A. Prevention of tuberculosis in macaques after intravenous BCG immunization |
| title | Prevention of tuberculosis in macaques after intravenous BCG immunization |
| title_full | Prevention of tuberculosis in macaques after intravenous BCG immunization |
| title_fullStr | Prevention of tuberculosis in macaques after intravenous BCG immunization |
| title_full_unstemmed | Prevention of tuberculosis in macaques after intravenous BCG immunization |
| title_short | Prevention of tuberculosis in macaques after intravenous BCG immunization |
| title_sort | prevention of tuberculosis in macaques after intravenous bcg immunization |
| url | https://hdl.handle.net/1721.1/128216 |
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