Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles.
Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles.
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DOI：
10.1016/j.actbio.2013.06.006
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发表时间：
2013-09
影响因子：
9.7
通讯作者：
Narasimhan, Balaji
中科院分区：
文献类型：
--
作者：
Haughney, Shannon L.;Petersen, Latrisha K.;Schoofs, Amy D.;Ramer-Tait, Amanda E.;King, Janice D.;Briles, David E.;Wannemuehler, Michael J.;Narasimhan, Balaji
肺炎球菌表面蛋白A （PspA）是一种胆碱结合蛋白，是在所有肺炎链球菌菌株表面发现的毒力因子。接种PspA疫苗已被证明对肺炎链球菌的致命攻击具有保护作用，使其成为一种有希望用于疫苗的免疫原。本文描述了利用聚酸酐纳米颗粒作为递送平台，设计一种基于pspa的亚单位疫苗。以己二酸（SA）、1,6-二-（对羧基苯氧基）己烷（CPH）和1,8-二-（对羧基苯氧基）-3,6-二氧基辛烷（CPTEG）为基材，分别以50:50 CPTEG:CPH和20:80 CPH:SA为基材，包封并释放PspA。从纳米颗粒配方中释放的蛋白质保留了其一级和二级结构以及抗原性。释放的PspA还具有生物学功能，基于其与载脂蛋白铁蛋白结合并阻止其对大肠杆菌的杀菌活性的能力。当PspA纳米颗粒制剂皮下注射到小鼠时，动物引起高滴度和高亲和力的抗PspA抗体反应。总之，这些研究为合理设计基于聚酸酐纳米颗粒的肺炎链球菌疫苗提供了框架。
Pneumococcal surface protein A (PspA) is a choline-binding protein which is a virulence factor found on the surface of all Streptococcus pneumoniae strains. Vaccination with PspA has been shown to be protective against a lethal challenge with S. pneumoniae, making it a promising immunogen for use in vaccines. Herein, the design of a PspA-based subunit vaccine using polyanhydride nanoparticles as a delivery platform is described. Nanoparticles based on sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy)hexane (CPH) and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG), specifically 50:50 CPTEG:CPH and 20:80 CPH:SA, were used to encapsulate and release PspA. The protein released from the nanoparticle formulations retained its primary and secondary structure as well as its antigenicity. The released PspA was also biologically functional based on its ability to bind to apolactoferrin and prevent its bactericidal activity towards Escherichia coli. When the PspA nanoparticle formulations were administered subcutaneously to mice, the animals elicited a high titer and high avidity anti-PspA antibody response. Together, these studies provide a framework for the rational design of a vaccine against S. pneumoniae based on polyanhydride nanoparticles.
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影响因子：
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作者：
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通讯作者：
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