Room Temperature Stable PspA-Based Nanovaccine Induces Protective Immunity.
Room Temperature Stable PspA-Based Nanovaccine Induces Protective Immunity.
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DOI：
10.3389/fimmu.2018.00325
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发表时间：
2018
影响因子：
7.3
通讯作者：
Narasimhan B
中科院分区：
文献类型：
--
作者：
Wagner-Muñiz DA;Haughney SL;Kelly SM;Wannemuehler MJ;Narasimhan B
肺炎链球菌是肺炎的主要病原体，肺炎是一种使人衰弱的疾病，特别是在年轻和老年人群中，并且是五岁以下儿童死亡的主要全球原因。虽然已有针对S. pneumoniae，没有一种对所有血清型都有保护作用。肺炎球菌表面蛋白A（PspA）是肺炎链球菌的关键毒力因子。肺炎球菌的荚膜抗原是一种抗原，其可以被掺入未来的疫苗中以解决由荚膜抗原的多样性所带来的免疫学挑战。PspA已被证明是免疫原性的，并能够启动体液免疫应答，该应答在大约94%的肺炎球菌菌株中是反应性的。可生物降解的聚酸酐已经被研究作为基于纳米颗粒的疫苗（即，纳米疫苗）平台以稳定不稳定蛋白质，提供佐剂性，并通过在单剂量中提供保护性免疫来增强患者依从性。在这项研究中，我们设计了一种室温稳定的基于PspA的聚酸酐纳米疫苗，其消除了对游离蛋白质组分的需要（即，100%包封在纳米颗粒内）。小鼠用先导纳米疫苗免疫一次，并且在攻击后，呈现出比仅用可溶性蛋白免疫的动物显著更高的存活率，即使蛋白剂量减少25倍。这种先导纳米疫苗制剂的表现与用明矾佐剂化的蛋白质相似，然而，在免疫部位具有少得多的组织反应原性。通过从纳米疫苗制剂中消除游离的PspA，先导纳米疫苗在室温下干燥储存60天后是有效的，打破了维持冷链的需要。总之，这项研究表明，单剂量的基于PspA的针对S.肺炎克雷伯氏菌诱导保护性免疫，并在室温下储存至少60天时提供热稳定性。
Streptococcus pneumoniae is a major causative agent of pneumonia, a debilitating disease particularly in young and elderly populations, and is the leading worldwide cause of death in children under the age of five. While there are existing vaccines against S. pneumoniae, none are protective across all serotypes. Pneumococcal surface protein A (PspA), a key virulence factor of S. pneumoniae, is an antigen that may be incorporated into future vaccines to address the immunological challenges presented by the diversity of capsular antigens. PspA has been shown to be immunogenic and capable of initiating a humoral immune response that is reactive across approximately 94% of pneumococcal strains. Biodegradable polyanhydrides have been studied as a nanoparticle-based vaccine (i.e., nanovaccine) platform to stabilize labile proteins, to provide adjuvanticity, and enhance patient compliance by providing protective immunity in a single dose. In this study, we designed a room temperature stable PspA-based polyanhydride nanovaccine that eliminated the need for a free protein component (i.e., 100% encapsulated within the nanoparticles). Mice were immunized once with the lead nanovaccine and upon challenge, presented significantly higher survival rates than animals immunized with soluble protein alone, even with a 25-fold reduction in protein dose. This lead nanovaccine formulation performed similarly to protein adjuvanted with Alum, however, with much less tissue reactogenicity at the site of immunization. By eliminating the free PspA from the nanovaccine formulation, the lead nanovaccine was efficacious after being stored dry for 60 days at room temperature, breaking the need for maintaining the cold chain. Altogether, this study demonstrated that a single dose PspA-based nanovaccine against S. pneumoniae induced protective immunity and provided thermal stability when stored at room temperature for at least 60 days.