Chemical & Biological Engineering, Iowa State University, Ames, IA 50011, USA.
Biomater Sci. 2019 Feb 26;7(3):809-821. doi: 10.1039/c8bm01443d.
Immunosenescence poses a formidable challenge in designing effective influenza vaccines for aging populations. While approved vaccines against influenza viruses exist, their efficacy in older adults is significantly decreased due to the diminished capabilities of innate and adaptive immune responses. In this work, the ability of a combination nanovaccine containing both recombinant hemagglutinin and nucleoprotein to provide protection against seasonal influenza virus infection was examined in young and aged mice. Vaccine formulations combining two nanoadjuvants, polyanhydride nanoparticles and pentablock copolymer micelles, were shown to enhance protection against challenge compared to each adjuvant alone in young mice. Nanoparticles were shown to enhance in vitro activation of dendritic cells isolated from aged mice, while both nanoadjuvants did not induce proinflammatory cytokine secretion which may be detrimental in aged individuals. In addition, the combination nanovaccine platform was shown to induce demonstrable antibody titers in both young and aged mice that correlated with the maintenance of body weight post-challenge. Collectively, these data demonstrate that the combination nanovaccine platform is a promising technology for influenza vaccines for older adults.
免疫衰老给设计针对老年人群体的有效流感疫苗带来了巨大挑战。尽管已经有针对流感病毒的批准疫苗，但由于先天和适应性免疫反应能力下降，它们在老年人中的效果明显降低。在这项工作中，研究了含有重组血凝素和核蛋白的组合纳米疫苗在年轻和老年小鼠中预防季节性流感病毒感染的能力。与每种佐剂单独使用相比，结合两种纳米佐剂（聚酸酐纳米颗粒和五嵌段共聚物胶束）的疫苗配方显示出对年轻小鼠的保护作用增强。研究表明，纳米颗粒可增强从老年小鼠中分离出的树突状细胞的体外激活，而两种纳米佐剂均不会诱导可能对老年人有害的促炎细胞因子分泌。此外，研究还表明，组合纳米疫苗平台可在年轻和老年小鼠中诱导可检测的抗体滴度，这与接种后体重的维持有关。总的来说，这些数据表明，组合纳米疫苗平台是一种有前途的针对老年人的流感疫苗技术。
