TB vaccine development has suffered from a lack of understanding of the determinants of immunity against Mtb infection. BCG, the current standard for TB vaccination, is effective at preventing severe forms of TB in young children, but does not reliably prevent pulmonary TB in adults 2. While TB is curable, the intensive antibiotic regimen coupled with the rise in antibiotic resistance underscores the need for an efficacious vaccine to help mitigate the global TB epidemic. M tb, the causative agent of TB, was responsible for the death of an estimated 1.4 million individuals in 2019 (ref. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB. Finally, an Mtb-specific IgM monoclonal antibody reduced Mtb survival in vitro. IgM was also enriched in macaques that received protective vaccination with an attenuated strain of Mtb. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. Intravenous (i.v.) vaccination with Bacille Calmette–Guérin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection against Mycobacterium tuberculosis ( Mtb).
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