DNA origami vaccines program antigen-focused germinal centers.

Recruitment and expansion of rare precursor B cells in germinal centers (GCs) is a central goal of vaccination to generate broadly neutralizing antibodies (bnAbs) against challenging pathogens such as HIV. Multivalent immunogen display is a well-established method to enhance vaccine-induced B cell responses, typically accomplished by using natural or engineered protein scaffolds. However, these scaffolds themselves are targets of antibody responses, with the potential to generate competitor scaffold-specific B cells that could theoretically limit expansion and maturation of "on-target" B cells in the GC response.