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

被引：11

作者：

Anish, Chakkumkal ^{[1
]}

Khan, Naeem ^{[2
]}

Upadhyay, Arun Kumar ^{[1
]}

Sehgal, Lleyinder ^{[2
]}

Panda, Amulya Kumar ^{[1
]}

机构：

[1] Natl Inst Immunol, New Delhi 110067, India

[2] Natl Inst Immunol, Mol Immunol Lab, New Delhi 110067, India

来源：

MOLECULAR PHARMACEUTICS | 2014年 / 11卷 / 03期

关键词：

pneumococcal capsular polysaccharides; antigen-delivery systems; polylactide nanoparticles; opsonophagocytic assay; memory antibody; pneumococcal surface antigen A (PsaA); pneumococcal surface protein A (PspA); INDUCED EPITOPIC SUPPRESSION; ANTIBODY-RESPONSE; VACCINE DELIVERY; ANTIGEN RELEASE; DENDRITIC CELLS; MICROPARTICLES; MACROPHAGES; POTENT; IMMUNIZATION; PARTICULATE;

D O I：

10.1021/mp400589q

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：922 / 937

页数：16

共 46 条

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