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.
Product Development Cell, ‡Molecular Immunology Laboratory, National Institute of Immunology , Aruna Asaf Ali Marg, New Delhi 110067, India.
Chakkumkal
C
Anish
Naeem
N
Khan
Arun Kumar
AK
Upadhyay
Devinder
D
Sehgal
Amulya Kumar
AK
Panda
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007114:Immunization; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D011108:Polymers / Q000737:chemistry*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage* / Q000276:immunology*
D009895:Opsonin Proteins; D022242:Pneumococcal Vaccines; D011108:Polymers; D011135:Polysaccharides, Bacterial
antigen-delivery systems; memory antibody; opsonophagocytic assay; pneumococcal capsular polysaccharides; pneumococcal surface antigen A (PsaA); pneumococcal surface protein A (PspA); polylactide nanoparticles