Therapeutic efficacy by pulmonary delivery of live attenuated mycobacteria

A prophylactic method for targeting M2 macrophages to alleviate an allergic response in a human subject in need thereof, comprising administering a composition to the subject through a pulmonary route by oral inhalation using an aerosol technique, wherein the composition comprises a live-attenuated M. tuberculosis comprising an isolated microorganism belonging to a M. tuberculosis MTBVAC strain having:

• i) a PhoP− phenotype by inactivation by genetic deletion of the Rv0757 gene, wherein the open-reading frame (ORF) sequence of phoP consists of SEQ ID NO:4, and ii) a deletion of a second gene, Rv2930 (fadD26), that prevents PDIM production, wherein the open-reading frame (ORF) sequence of fadD26 consists of SEQ ID NO:2;
• wherein the composition is administered at a dose of at least 106 CFUs;
• and
• wherein the subject is at risk of suffering from allergic asthma, or at risk of developing allergic asthma.