Protein engineering and particulate display of B-cell epitopes to facilitate development of novel vaccines

Induction of antigen-specific humoral immunity is a correlate of protection for many diseases and remains a primary vaccine goal. Pathogens can evade such responses by limiting epitope access, by diversifying surface residues, or by keeping antigens in metastable conformations. B cells can target diverse epitopes on an antigen, but only a subset of which produce functional antibodies. Structure-based immunogen engineering can help overcome these hurdles by using structural information for targeted induction of particular antibodies while improving the overall vaccine immunogenicity. This review will cover recent progress in vaccine design, specifically focusing on strategies to stabilize antigens for optimal B-cell epitope exposure, engineer synthetic B-cell epitopes to induce antibodies with specific features and enhancement of vaccine potency through antigen presentation on multivalent particles.