LAUSR

Lymph node follicles capture and retain antigens to induce germinal centers and long-lived humoral immunity. However, control of antigen retention has been limited. Here we discovered that antigen conjugated to different sizes of nanoparticle carrier impacts the intra-lymph node transport and specific cell interaction. We found that follicular dendritic cell (FDC) networks determine the intra-lymph node follicle fate of these nanoparticles by clearing smaller ones (5-15 nm) within 48 hours and retaining larger ones (50-100 nm) for over 5 weeks. The cause of the differential retention is due to the adsorption of complement C3 onto larger nanoparticles that led to greater interactions with receptors on the FDC dendrites. Because of these findings, we can use the size of the nanoparticle carrier to manipulate the retention time of antigens, where the 50-100 nm sized nanoparticles had 175-fold more delivery of antigen at the FDC dendrites, 5-fold enhanced humoral immune responses of germinal center B cell formation, and 5-fold more antigen-specific antibody production over 5-15 nm nanoparticles. Our results show that we can tune humoral immunity by simply manipulating the carrier size design to produce effectiveness of vaccines.