Environmental effects on protection against Mycobacterium tuberculosis after immunization with Ad85A

► The environment alters the immune response to an intradermal (i.d.) TB subunit vaccine, Ad85A. ► Ad85A i.d. induces a lung immune response but is less protective against Mtb than intranasal Ad85A. ► Oral administration of environmental mycobacteria reduces Ad85A i.d induced protection. ► In vivo depletion of CD25+ regulatory T cells abolishes the effect of oral mycobacteria.