Zhang Jiarui, Liu Yian, Bai Lintao, Gao Gan, Li Yuxuan, Shen Heyun
Beijing Key Laboratory of Bioprocess, Beijing University of Chemical Technology, Beijing, 100029, China.
Macromol Biosci. 2023 May;23(5):e2200520. doi: 10.1002/mabi.202200520. Epub 2023 Apr 6.
Adjuvants are widely used in vaccine to improve the protection or treatment efficacy. However, so far they inevitably produce side effects and are hard to induce cellular immunity in practical application. Herein, two kinds of amphiphilic poly(glutamic acid) nanoparticles (α-PGA-F and γ-PGA-F NPs) as nanocarrier adjuvants are fabricated to induce an effective cellular immune response. Amphiphilic PGA are synthesized by grafting phenylalanine ethyl ester to form biodegradable self-assembly nanoadjuvants in a water solution. The model antigen, chicken ovalbumin (OVA), can be loaded into PGA-F NPs (OVA@PGA-F NPs) with the high loading ratio >12%. Moreover, compared with γ-PGA-F NPs, the acidic environment can induce the α-helical secondary structure of α-PGA NPs, promoting membrane fusion and more fast antigen lysosomal escape. Hence, the antigen presenting cells treated with OVA@α-PGA-F NPs show higher secretion of inflammatory cytokines, and higher expression of major biological histocompatibility complex class I and CD80 than those of OVA@γ-PGA-F NPs. Overall, this work indicates that pH responsive α-PGA-F NPs as a carrier adjuvant can effectively improve the ability of cellular immune responses, leading to it being a potent candidate for vaccine applications.
佐剂在疫苗中被广泛使用以提高保护或治疗效果。然而，到目前为止，它们在实际应用中不可避免地会产生副作用，并且难以诱导细胞免疫。在此，制备了两种两亲性聚谷氨酸纳米颗粒（α-PGA-F和γ-PGA-F NPs）作为纳米载体佐剂，以诱导有效的细胞免疫反应。通过接枝苯丙氨酸乙酯合成两亲性聚谷氨酸，在水溶液中形成可生物降解的自组装纳米佐剂。模型抗原鸡卵清蛋白（OVA）可以以大于12%的高负载率负载到PGA-F NPs（OVA@PGA-F NPs）中。此外，与γ-PGA-F NPs相比，酸性环境可以诱导α-PGA NPs的α-螺旋二级结构，促进膜融合并使抗原更快地从溶酶体中逃逸。因此，用OVA@α-PGA-F NPs处理的抗原呈递细胞比OVA@γ-PGA-F NPs表现出更高的炎性细胞因子分泌以及主要组织相容性复合体I类和CD80的更高表达。总体而言，这项工作表明pH响应性α-PGA-F NPs作为载体佐剂可以有效提高细胞免疫反应能力，使其成为疫苗应用的有力候选者。
