Antigen spacing on protein nanoparticles influences antibody responses to vaccination.

Computational design of a closed trimeric HA head ("trihead") antigen platform.Design of a rigid, extendable linker between displayed antigen and underlying protein nanoparticle enables precise variation of antigen spacing.Decreased antigen spacing of triheads elicits antibodies with the highest HAI, neutralizing activity, and cross-reactivity.Changes to antigen spacing alter epitope specificities of vaccine-elicited antibodies.