PT - JOURNAL ARTICLE AU - Edna George AU - Avijit Goswami AU - Tejan Lodhiya AU - Priyanka Padwal AU - Shalini Iyer AU - Iti Gauttam AU - Lakshay Sethi AU - Sharumathi Jeyasankar AU - Pallavi Raj Sharma AU - Ameya Atul Dravid AU - Raju Mukherjee AU - Rachit Agarwal TI - Immunomodulatory effect of mycobacterial outer membrane vesicles coated nanoparticles AID - 10.1101/2022.06.07.495204 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.06.07.495204 4099 - http://biorxiv.org/content/early/2022/06/08/2022.06.07.495204.short 4100 - http://biorxiv.org/content/early/2022/06/08/2022.06.07.495204.full AB - Tuberculosis (TB) is one of the most widely prevalent infectious diseases that cause significant mortality. Bacillus Calmette-Guérin (BCG), the current TB vaccine used in clinics, shows variable efficacy and has safety concerns for immunocompromised patients. There is a need to develop new and more effective TB vaccines. Outer membrane vesicles (OMVs) are vesicles released by Mycobacteria that contain several lipids and membrane proteins and act as a good source of antigens to prime immune response. However, the use of OMVs as vaccines has been hampered by their heterogeneous size and low stability. Here we report that mycobacterial OMVs can be stabilized by coating over uniform-sized 50 nm gold nanoparticles. The OMV-coated gold nanoparticles (OMV-AuNP) show enhanced uptake and activation of macrophages and dendritic cells. Proteinase K and TLR inhibitor studies demonstrated that the enhanced activation was attributed to proteins present on OMVs and was mediated primarily by TLR2 and TLR4. Mass spectrometry analysis revealed several potential membrane proteins that were common in both free OMVs and OMV-AuNP. Such strategies may open up new avenues and the utilization of novel antigens for developing TB vaccines.Competing Interest StatementThe authors have declared no competing interest.