ManLAM-aptamer as an immunoadjuvant improves immune-protective effects of BCG (VAC7P.968)

Abstract Tuberculosis (TB) remains an important worldwide health threat. However vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG), the only available licensed vaccine of TB, provides limited protection against adult pulmonary tuberculosis. Mannosylated lipoarabinomannan (ManLAM) is a kind of glycolipid on the cell wall surface of BCG and has been implicated with remarkable immunosuppressive effect on the host immune cells. In the present study, we used Systematic Evolution of Ligands by EXponential enrichment (SELEX) to generate a single-stranded DNA aptamer that specifically bound to ManLAM of BCG with high affinity. We found that vaccination with BCG combined with BM2 recruited dendritic (DC) cells into peripheral lymph nodes and decreased the numbers of regulatory B cells and regulatory T cells. It could also significantly enhanced the Th1-type cellular response and induced conversion of IgG2a isoforms in mice. We demonstrated that vaccination with BCG plus BM2 significantly reduced the progression of Mycobacterial tuberculosis (M. tb) H37Rv infection, bacterial loads in lungs and spleens of mice via aerosol infection with M. tb H37Rv, and provided much better protective immune response against M. tb than vaccination with BCG alone. Our data provide a new strategy for TB control and the aptamer BM2 holds great promise for developing a new potential immunoadjuvant of BCG.