M. smegmatis IKEPLUS Immunization Reveals the Mycobacterial Ribosome as a Source of Novel CD4+ T cell Antigens
Kennedy, Steven C.
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No vaccine candidate has had major success in reducing the enormous global burden of disease due to Mycobacterium tuberculosis (Mtb). Critical to the control of Mtb is the ability of a vaccine to induce a strong CD4+ Tcell response. The current standard vaccination against Mtb, M. bovis BCG, is of limited efficacy, potentially due to its retention of pathogenic mechanisms that actively inhibit the host presentation of critical antigens to CD4+Tcells. Our lab has used an attenuated M.Smegmatis, IKEPLUS, to investigate the CD4+ Tcell response to non-pathogenic mycobacteria. Non-pathogenic mycobacteria do not inhibit presentation of antigens to CD4+Tcells, and therefore may expose cryptic antigens for vaccination. Examination of the CD4 + Tcell response to IKEPLUS and BCG has identified the mycobacterial ribosome as a major immunogenic target in M. smegmatis based vaccination, but not in BCG. This dichotomy in the immune response led us to further characterize the ribosome and evaluate its protein constituents as potential vaccine targets. We have identified 24 of the total 57 mycobacterial ribosomal proteins as significantly immunogenic and have identified minimal CD4+ Tcell epitopes for 10 of the 24 ribosomal proteins. Furthermore, one protein, RpIJ, has shown particularly strong CD4+Tcell responses in mice immunized with recombinant protein, whole M. Smegmatis, and in the lungs of immunized mice followed by challenge with Mtb. Mycobacterial ribosomal proteins represent a new set of mycobacterial antigens that could augment the current BCG vaccination and protect against Mtb.