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Bacillus Calmette\u2010Guerin (BCG), the only licensed vaccine against TB protects against severe disseminated forms of TB in infants but shows poor efficacy against pulmonary TB in adults. Co\u2010infections have been reported as one of the factors implicated in vaccine inefficacy. Given the geographical overlap of malaria and TB in areas where BCG vaccination is routinely administered, we hypothesized that virulence\u2010dependent co\u2010infection with Plasmodium species could alter the BCG\u2010specific immune responses thus resulting in failure to protect against Mycobacterium tuberculosis. We compared virulent <jats:italic>Plasmodium berghei<\/jats:italic> and non\u2010virulent <jats:italic>Plasmodium chabaudi<\/jats:italic>, their effects on B cells, effector and memory T cells, and the outcome on BCG\u2010induced efficacy against <jats:italic>M<\/jats:italic>.\u00a0<jats:italic>tuberculosis<\/jats:italic> infection. We demonstrate that malaria co\u2010infection modulates both B\u2010 and T\u2010cell immune responses but does not significantly alter the ability of the BCG vaccine to inhibit the growth of <jats:italic>M<\/jats:italic>.\u00a0<jats:italic>tuberculosis<\/jats:italic> irrespective of parasite virulence. This malaria\u2010driven immune regulation may have serious consequences in the early clinical trials of novel vaccines, which rely on vaccine\u2010specific T\u2010cell responses to screen novel vaccines for progression to the more costly vaccine efficacy trials.<\/jats:p>","DOI":"10.1111\/imm.13431","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T17:02:00Z","timestamp":1636909320000},"page":"219-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["BCG\u2010mediated protection against <i>M. tuberculosis<\/i> is sustained post\u2010malaria infection independent of parasite virulence"],"prefix":"10.1111","volume":"165","author":[{"given":"Emily","family":"Tangie","sequence":"first","affiliation":[{"name":"Division of Immunology Department of Pathology Institute of Infectious Disease and Molecular Medicine Health Sciences Faculty University of Cape Town  Observatory South 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