BCG vaccination in childhood is not related to pulmonary immunity against M. tuberculosis in adults

Background: Neonatal vaccination with Mycobacterium bovis Bacille Calmette-Guérin (BCG) reduces the risk of infection with M. tuberculosis and the risk for severe forms of tuberculosis in children. Objectives: Evaluation of the effect of neonatal M. bovis BCG vaccination on sensitization with M. tuberculosis antigens in adults. Methods: Adult healthy M. tuberculosis exposed healthcare workers and household tuberculosis contacts and cured tuberculosis patients were recruited. Interferon-g release assays (IGRAs) were performed on blood and mononuclear cells from bronchoalveolar-lavage (BALMC). BALMC were co-cultured with M. tuberculosis in growth inhibition assays. Results: 512 individuals with known M. bovis BCG vaccination status were recruited. Of 505 HIV-uninfected, 322 (64%) were vaccinated, while 183 (36%) were not. In 170 of 483 contacts with known blood IGRA status, the IGRA result was positive. Of the 88 subjects from which a BALMC IGRA was performed, 26 had a positive result. M. tuberculosis-specific IGRA responses were not associated with M. bovis BCG vaccination status (ORs were 1.09, P= 0.66, and 0.81, P= 0.68, for blood and BAL respectively). The frequency of PPD responsive BAL mononuclear cells was higher in vaccinated versus non-vaccinated persons with a median (IQR) of 22 (6-101) versus 8 (1-44) spot forming cells per 200.000 BALMC, respectively (P=0.0468). In BALMC based growth inhibition assays, M. tuberculosis growth rates did not differ between M. bovis BCG-vaccinated and non-vaccinated subjects. Conclusions: Early childhood vaccination with M. bovis BCG does not protect from infection with M. tuberculosis in adulthood as defined by IGRA testing.