Poly(I:C)-Encapsulating Nanoparticles Enhance Innate Immune Responses to the Tuberculosis Vaccine Bacille Calmette–Guérin (BCG) via Synergistic Activation of Innate Immune Receptors

The attenuated live vaccine strain Bacille Calmette-Guerin (BCG) is currently the only available vaccine against tuberculosis (TB), but is largely ineffective against adult pulmonary TB, the most common disease form. This is in part due to BCG’s ability to interfere with the host innate immune response, a feature that might be targeted to enhance the potency of this vaccine. Here, we investigated the ability of chitosan-based nanoparticles (pIC-NPs) containing polyinosinic-polycytidylic acid (poly(I:C)), an inducer of innate immunity via Toll-like receptor 3 (TLR3) to enhance the immunogenicity of BCG in mouse bone marrow-derived macrophages (BMDM) in vitro. Incorporation of poly(I:C) into NPs protected it against degradation by ribonucleases and increased its uptake by mouse BMDM. Whereas soluble poly(I:C) was ineffective, pIC-NPs strongly enhanced the pro-inflammatory immune response of BCG-infected macrophages in a synergistic fashion, as evident by increased production of cytokines and induction of ni...