Immunogenicity Studies with Microbial Fractions of M. tuberculosis H37Rv Total Culture Filtrate

Current study investigates the whole secretory proteome of Mycobacterium tuberculosis as culture filtrate fractions to identify immunoprotective protein antigens on the basis of protection studies in animal (mouse and guinea pig) models. Secretory culture filtrate proteins (CFPs) of M. tuberculosis H37Rv were fractionated into fifteen narrow molecular mass fractions in the order of increasing molecular size (F1-F15) by electroelution. Immunization studies revealed proteins in the molecular weight range of 20-24kDa (F7), 25-30kDa (F8) and 37-42kDa (F11) as key protective fractions against experimental tuberculosis in both the animal (mice and guinea pig) models. Amongst these fractions, F7 imparted even better protection as compared to BCG. Immunological studies with all the fractions demonstrated that although selected three protective fractions were able to induce significant immune responses in both short term culture filtrate (STCF) immunized and Mtb infected animals, there were number of other non-protective fractions also that were inducing higher immune responses either in immunized animals (e.g.F12-F15) or in Mtb challenged animals (e.g.F1-F6). These results demonstrate that only those mycobacterial proteins that are recognized by the host immune system both during immunization and infection can induce significant protection against experimental tuberculosis, however there is no direct correlation between the level of immune responses and degree of protective efficacy.