Delivery of Polysaccharides Using Polymer Particles: Implications on Size-Dependent Immunogenicity, Opsonophagocytosis, and Protective Immunity

Bacterial capsular polysaccharides are components of many modern vaccines, but they are weakly immunogenic. Herein, we describe the delivery of pneumococcal capsular polysaccharide serotype-1 (PCP-1) in polylactide polymeric particles to enhance its immunogenicity. Immunization with PCP-1-entrapped particles elicited long-term memory antibody responses from a single intramuscular injection. PCP-1-entrapped nanoparticles (NPs) elicited significantly higher anti-PCP-1 IgG responses than that observed with soluble and microparticles (MPs) formulations. Delivering PCP-1 and pneumococcal proteins in same particles did not improve the IgG response. The sera of animals immunized with PCP-1-entrapped particles promoted efficient opsonophagocytosis of pneumococci by macrophages. Single-dose immunization with PCP-1-entrapped particles conferred a long-term serotype-specific protection against lethal pneumococcal challenge. The higher immunogenicity of PCP-1 nanoparticles showed correlation with enhanced uptake by antigen-presenting cells. The results highlight the potential of polymeric nanoparticles as an efficient means of presenting polysaccharide antigens to the immune system.