Nanoparticles have been shown to enhance the immune response to subunit protein antigens for efficacious vaccinations. The role of particle size in transport from the site of administration to the draining lymph node has been widely investigated. Studies have consistently shown that smaller sized particles, ≤25 nm, are rapidly transported to the draining lymph node, while larger sized particles, ≥100 nm, are transported more slowly. However, the impact of the polymer chemistry and the initial particle size on the transport of these formulations to the lymph node and on the corresponding immune response has not been studied in detail.
Our group has investigated the use of subunit antigens encapsulated into polyanhydride nanoparticles as a vehicle for vaccine delivery and as an adjuvant for the immune response. This has been demonstrated through the effectiveness of a single intranasal administration of a nanoparticle formulation containing soluble and encapsulated Yersinia pestis fusion proteins, F1-V, which was protective against a lethal challenge.
In this work we investigate the role of polyanhydride nanoparticle chemistry on the transport of antigen to the lymph node distal from the administration site. The kinetics of soluble and encapsulated antigen delivery to the lymph node and the cellular context were investigated. The role of polymer chemistry on antigen presenting cell internalization and subsequent transport to and localization within the distal lymph node was investigated using a combination of flow cytometry and confocal microscopy. Our results will provide insights into the design of antigen carrier devices needed to impart an efficacious vaccine formulation, and the potential to direct the immune response toward either antibody-mediated or cell-mediated immunity.