Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques

For many pathogens, including most targets of effective vaccines, infection elicits an immune response that confers significant protection against reinfection.There has been significant debate as to whether natural Mycobacterium tuberculosis (Mtb) infection confers protection against reinfection.Here we experimentally assessed the protection conferred by concurrent Mtb infection in macaques, a robust experimental model of human tuberculosis (TB), using a combination of serial imaging and Mtb challenge strains differentiated by DNA identifiers.Strikingly, ongoing Mtb infection provided complete protection against establishment of secondary infection in over half of the macaques and allowed near sterilizing bacterial control for those in which a secondary infection was established.By contrast, boosted BCG vaccination reduced granuloma inflammation but had no impact on early granuloma bacterial burden.These findings are evidence of highly effective concomitant mycobacterial immunity in the lung, which may inform TB vaccine design and development. Author summaryTuberculosis (TB), a lung disease caused by the bacterial pathogen Mycobacterium tuberculosis, is endemic in many developing countries.This infection is transmitted from a person with active tuberculosis through coughing, talking, and singing.Exposure to this bacterium can result in a spectrum of infection outcomes, including in the majority of persons asymptomatic infection, known as latent TB.However, re-exposure to those with active disease occurs frequently, particularly in crowded conditions.Here we demonstrate