Rational design of PLGA nanoparticles vaccine delivery systems to improve immune responses.

Nanoparticles-based vaccine delivery systems have been extensively used to promote and induce immune responses to protein antigens. The property of the nanoparticles, such as size, surface charge and antigen loading mode, have been proved to significantly influence the adjuvant effect and immunoreactivity of nanoparticles-based vaccine delivery systems. The purpose of the study was to investigate how surface charge and antigen loading modes of nanoparticles impact the immune responses. In this study, three OVA-loaded PLGA nanoparticles with different surface charges and antigen loading modes were developed. The three nanoparticles were designed as antigen-encapsulated with negatively charged (ASP-PLGA/OVA), antigen-encapsulated with PEI-coated (ASP-PLGA/OVA-PEI) and antigen-adsorbed on PEI-coated nanoparticles (ASP-PLGA-PEI-OVA). The Angelica sinensis polysaccharide (ASP) was used as the immunopotentiator and encapsulated into three nanoparticles. The results demonstrated that both PEI-coated (positively charged) nanoparticles promoted the antigen escape from the endosome, which led to the cytoplasmic antigen delivery to generate cross-presentation, compared to negatively charged nanoparticles. In addition, PEI-coated nanoparticles activated the DCs in lymph nodes at five days after the primary vaccination. In vivo experiments demonstrated that both antigen-encapsulated nanoparticles induced more potent and long-term antigen-specific antibody responses, compared to antigen-adsorbed nanoparticles. Thus, the PEI-coated and antigen-encapsulated nanoparticles (ASP-PLGA/OVA-PEI) as a vaccine adjuvant delivery system has the potential to induce strong and long-term humoral and cellular immune responses.