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首页> 外文期刊>Acta biomaterialia >Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles
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Retention of structure, antigenicity, and biological function of pneumococcal surface protein A (PspA) released from polyanhydride nanoparticles

机译：保留从聚酸酐纳米颗粒释放的肺炎球菌表面蛋白A（PspA）的结构，抗原性和生物学功能

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摘要

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 against Escherichia coli. When the PspA nanoparticle formulations were administered subcutaneously to mice they 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.
机译：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上发现的一种致病因子。 PspA疫苗已被证明可以抵抗肺炎链球菌的致死性攻击，使其成为用于疫苗的有希望的免疫原。本文描述了使用聚酸酐纳米颗粒作为递送平台的基于PspA的亚单位疫苗的设计。基于癸二酸（SA），1,6-双-（对羧基苯氧基）己烷（CPH）和1,8-双-（对羧基苯氧基）-3,6-二氧八辛烷（CPTEG）的纳米颗粒，特别是50:50 CPTEG：CPH和20:80 CPH：SA用于封装和释放PspA。从纳米颗粒制剂中释放的蛋白质保留其一级和二级结构以及其抗原性。释放的PspA还具有结合脱铁乳铁蛋白并防止其对大肠杆菌的杀菌活性的能力，因此具有生物学功能。当将PspA纳米颗粒制剂皮下给予小鼠时，它们引起高滴度和高亲和力的抗PspA抗体应答。这些研究共同为基于聚酸酐纳米颗粒的肺炎链球菌疫苗的合理设计提供了框架。

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