Self-Adjuvanting\nAdenoviral Nanovaccine for Effective\nT‑Cell-Mediated Immunity and Long-Lasting Memory Cell Activation\nagainst Tuberculosis

An enhanced vaccine is immediately required to swap the\nmore than\n100 year-old bacillus Calmette-Guerin (BCG) vaccine against tuberculosis.\nHere, trimethyl chitosan-loaded inactivated Mycobacterium\nsmegmatis (MST), along with potent adenovirus hexon\nprotein (AdHP), and toll-like receptor (TLR)-1/2 as a nanovaccine,\nwas developed against tuberculosis (TB). The nanoformulation increased\nthe bioavailability of MST and elicited the targeting ability. Nanovaccines\nhave a size range of 183.5 ± 9.5 nm with a spherical morphology\nand uniform distribution. The nanovaccine exhibited a higher release\nof antigen in acidic pH, and this is mainly due to protonation of\nionizable groups in polymeric materials. The nanovaccine facilitated\nthe effective cellular uptake of bone-marrow-derived dendritic cells\nand progressive endosomal escape in a shorter period. In vitro analyses\nindicated that the nanovaccine activated cytokine and T-cell production\nand also assisted in humoral immunity by producing antibodies. The\nnanovaccine was able to induce more cellular and humoral memory cells\nand a better protective immune response. Nanomaterials effectively\ndelivered the MST, AdHP, and TLR1/2 antigens to the major histocompatibility\ncomplex class I and II pathways to generate protective cytotoxic CD8<sup>+</sup> and CD4<sup>+</sup> T-cells. In vivo experiments, compared\nwith free MST and BCG, showed that mice immunized with the nanovaccine\ninduced more specific CD4<sup>+</sup>, CD8<sup>+</sup>, and memory\nT-cell activations. Overall, the fabricated nanovaccine was able to\ncontrol the release of antigens and adjuvants and enhance memory cell\nactivation and humoral immunity against TB.