Tuberculosis (TB) is a communicable disease caused by Mycobacterium tuberculosis (Mtb) that is of global importance, particularly in low-income countries. It is spread through the nasal pharyngeal route and localizes in the alveolar macrophages of the lung, with 5-10% of infected individuals developing active TB disease. To combat this chronic airborne disease, there is an urgent need for better therapeutic prophylaxis and measures that are both effective and affordable. Vaccines are a cost-effective and safe prophylaxis, and Mycobacterium bovis bacillus Calmette-Guerin (M. Bovis BCG) is the only anti-tuberculosis vaccine available. There are 13 BCG strains in use today, but it is unclear why they elicit different immunological responses following vaccination.To better understand the immunological differences between the BCG vaccine strains, this study aims to use proteomics, Phosphoproteomics and Lipidomics to investigate the extent in which three clinical M. Bovis BCG vaccine strains (BCG Danish, BCG Pasteur and BCG Russia) differ from each other. We will analyze the molecular complexity of BCG - mammalian systems through mass spectrometry and correlate the observed changes with the differing immunological responses found in infants vaccinated with the different BCG strains.We hypothesize that the BCG strains will induce distinct immune responses and that these differences can be measured through mass spectrometric techniques. We observe differential protein expression in macrophage cells infected with the different BCG strains; Enriched pathways highlighting various lipid classes primarily driving the different macrophage immune responses. This research has the potential to inform decision-making around which BCG strain to use and to inform future vaccine development efforts.