Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype

被引:239
作者
Demento, Stacey L. [1 ]
Cui, Weiguo [2 ]
Criscione, Jason M. [1 ]
Stern, Eric [1 ]
Tulipan, Jacob [1 ]
Kaech, Susan M. [2 ]
Fahmy, Tarek M. [1 ]
机构
[1] Yale Univ, Dept Biomed Engn, New Haven, CT 06511 USA
[2] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06511 USA
基金
美国国家科学基金会;
关键词
Liposome; PLGA; Nanoparticle; Persistence; Vaccine; Memory T cells; IMMUNE-RESPONSES; DELIVERY SYSTEMS; ADJUVANTS; EFFECTOR; LIPOSOMES; DIFFERENTIATION; MICROSPHERES; LYMPHOCYTES; VACCINATION; ACTIVATION;
D O I
10.1016/j.biomaterials.2012.03.041
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Particulate vaccines are emerging promising technologies for the creation of tunable prophylactics against a wide variety of conditions. Vesicular and solid biodegradable polymer platforms, exemplified by liposomes and polyesters, respectively, are two of the most ubiquitous platforms in vaccine delivery studies. Here we directly compared the efficacy of each in a long-term immunization study and in protection against a model bacterial antigen. Immunization with poly(lactide-co-glycolide) (PLGA) nanoparticles elicited prolonged antibody titers compared to liposomes and alum. The magnitude of the cellular immune response was also highest in mice vaccinated with PLGA, which also showed a higher frequency of effector-like memory T cell phenotype, leading to an effective clearance of intracellular bacteria. The difference in performance of these two common particulate platforms is shown not to be due to material differences but appears to be connected to the kinetics of antigen delivery. Thus, this study highlights the importance of sustained antigen release mediated by particulate platforms and its role in the long-term appearance of effector memory cellular response. (c) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:4957 / 4964
页数:8
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