Directing vaccine immune responses to mucosa by nanosized particulate carriers encapsulating NOD ligands

Mucosal surfaces are a major portal of entry for many pathogens that are the cause of infectious diseases. Therefore, effective vaccines that induce a protective immune response at these sites are much needed. However, despite early success with the live attenuated oral polio vaccine over 50 years ago, only a few new mucosal vaccines have been subsequently licensed. Development of new adjuvants, comprising antigen delivery platforms and immunostimulatory molecules, are critical for the successful development of new mucosal vaccines. Among them, biodegradable nanoparticle delivery systems are promising and NOD-like receptors are considered as potential new targets for immunostimulatory molecules. In this work, different NOD1 and NOD2 ligands were encapsulated in polylactic acid (PLA) nanoparticles, coated with HIV-1 gag p24 antigen. We showed that these new formulations are able to induce proliferation of HIV-specific T cells from HIV(+) individuals as well as autophagy. In vivo, these formulations highly enhanced p24-specific systemic and mucosal immune responses in mice not only after mucosal administration but also after immunization via the parenteral route. Our results provide a rational approach for combining nanosized particulate carriers and encapsulated NOD receptor ligands as potent synergistic tools for induction of specific mucosal immunity.