Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation

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

Understanding the link between structural features of antigen display and immunological induction is vital in designing nanoparticulate vaccines. Multivalent interactions promote B-cell receptor (BCR) clustering and signaling and facilitate receptor-mediated internalization of antigen. Antigen features, such as epitope affinity, valency, or co-receptor recruitment can impact B and T cell signaling. In a study that used antigen-conjugated polymer to assay the impact of antigen valency on B cell activation, Puffer et al. showed that clustering of BCRs by multivalent antigens is crucial for antigen-dependent signaling. The antigen-conjugated polymers clustered unbound BCRs and contributed to enhanced intracellular signalling [176] . Whereas the multivalent antigen-polymer conjugates elicited antibody production, free antigens failed to trigger humoral responses (Fig. 4A) . Highly repetitive surfaces are also known to bind strongly to natural IgM antibodies through multivalent, high-avidity interactions [177] . Such antibody binding also facilitates cellular uptake of particles by macrophages and dendritic cells, which can in turn enhance immune processing through increased antigen presentation. It is also worth noting that many important components in the humoral arm of innate immunity, such as complement C1q, pentraxins, ficolins and collectins, are multimeric structures that favor high-avidity interactions with repetitive pathogen surfaces [178] (Fig. 4B) . These observations highlight how the immune system has been primed to respond to repetitive motifs frequently found on viral particles.