Abstract：
: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.
journal_name
Naturejournal_title
Natureauthors
Darrah PA,Zeppa JJ,Maiello P,Hackney JA,Wadsworth MH 2nd,Hughes TK,Pokkali S,Swanson PA 2nd,Grant NL,Rodgers MA,Kamath M,Causgrove CM,Laddy DJ,Bonavia A,Casimiro D,Lin PL,Klein E,White AG,Scanga CA,Shalek AK,Roededoi
10.1038/s41586-019-1817-8subject
Has Abstractpub_date
2020-01-01 00:00:00pages
95-102issue
7788eissn
0028-0836issn
1476-4687pii
10.1038/s41586-019-1817-8journal_volume
577pub_type
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