Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

Chattopadhyay, Saborni; Chen, Jui-Yi; Chen, Hui-Wen; Hu, Che-Ming Jack

Transport of viral antigen and immune-potentiating adjuvants by viruses to immune cells is a highly coordinated event as viral particles shuttle both antigen targets and adjuvanting nucleic acids simultaneously. Such antigen/adjuvant coordination, or its absence, has been shown to strongly influence immune cell activation [162] . In addition, the immune system can respond to viruses through multiple PAMPs, including glycoprotein, DNA, dsRNA, and ssRNA, activating a broad spectrum of signalling pathways for heightened antiviral immunity [163] . The synthetic flexibility of nanoparticles has thus been exploited to emulate the co-delivery capacity of viral pathogens to boost immune responses. In some cases, antigen and adjuvant are localized on the same nanoparticles for synchronized delivery. Ma et al. incorporated a hepatitis B surface antigen (HBsAg) and CpG adjuvant onto PLGA nanoparticles via conjugation with dopamine, allowing the particles to display both the viral antigen and the immune activator. The study showed that the pathogen-mimicking particle enhanced the recruitment of immune cells to the injected site, activated bone marrow derived dendritic cells, and induced strong humoral and cellular immune responses [164] . In another study conducted by Kuai et al., a disc-like synthetic high-density lipoprotein (sHDL) was applied to integrate both target antigens of CD8+ T cells and CpG-ODN for anticancer vaccination. The nanodisc drastically improved the co-delivery of antigens and adjuvants to lymph nodes compared to soluble vaccine and induced a 31-fold enhancement in antigen-specific CD8+ cytotoxic T-lymphocyte response as compared to the free peptide and adjuvant control.