Zhang Weifeng, Wang Lianyan, Liu Yuan, Chen Xiaoming, Li Jiahui, Yang Tingyuan, An Wenqi, Ma Xiaowei, Pan Ruowen, Ma Guanghui
National Key Laboratory of Biochemical Engineering PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering Chinese Academy of Sciences, Bei-Er-Jie No.1, Zhong-Guan-Cun, Haidian District, Beijing, 100190, People's Republic of China.
Pharm Res. 2014 Apr;31(4):1015-31. doi: 10.1007/s11095-013-1224-z. Epub 2013 Oct 30.
To compare the adjuvanticity of polymeric particles (new-generation adjuvant) and alum (the traditional and FDA-approved adjuvant) for H5N1 influenza split vaccine, and to investigate respective action mode.
Vaccine formulations were prepared by incubating lyophilized poly(lactic acid) (PLA) microparticles or alum within antigen solution. Antigen-specific immune responses in mice were evaluated using ELISA, ELISpot, and flow cytometry assay. Adjuvants' action modes were investigated by determining antigen persistence at injection sites, local inflammation response, antigen transport into draining lymph node, and activation of DCs in secondary lymphoid organs (SLOs).
Alum promoted antigen-specific humoral immune response. PLA microparticles augmented both humoral immune response and cell-mediated-immunity which might enhance cross-protection of influenza vaccine. With regard to action mode, alum adjuvant functions by improving antigen persistence at injection sites, inducing severe local inflammation, slightly improving antigen transport into draining lymph nodes, and improving the expression of MHC II on DCs in SLOs. PLA microparticles function by slightly improving antigen transport into draining lymph nodes, and promoting the expression of both MHC molecules and co-stimulatory molecules on DCs in SLOs.
Considering the adjuvanticity and side effects (local inflammation) of both adjuvants, we conclude that PLA microparticles are promising alternative adjuvant for H5N1 influenza split vaccine.
比较聚合物颗粒（新一代佐剂）和明矾（传统且获美国食品药品监督管理局批准的佐剂）对H5N1流感裂解疫苗的佐剂活性，并研究各自的作用方式。
通过将冻干的聚乳酸（PLA）微粒或明矾在抗原溶液中孵育来制备疫苗制剂。使用酶联免疫吸附测定（ELISA）、酶联免疫斑点测定（ELISpot）和流式细胞术分析评估小鼠体内的抗原特异性免疫反应。通过测定注射部位的抗原持久性、局部炎症反应、抗原向引流淋巴结的转运以及二级淋巴器官（SLOs）中树突状细胞（DCs）的激活来研究佐剂的作用方式。
明矾促进抗原特异性体液免疫反应。PLA微粒增强了体液免疫反应和细胞介导的免疫，这可能增强流感疫苗的交叉保护作用。关于作用方式，明矾佐剂通过提高注射部位的抗原持久性、诱导严重的局部炎症、略微改善抗原向引流淋巴结的转运以及提高SLOs中DCs上主要组织相容性复合体II类分子（MHC II）的表达来发挥作用。PLA微粒通过略微改善抗原向引流淋巴结的转运，并促进SLOs中DCs上MHC分子和共刺激分子的表达来发挥作用。
考虑到两种佐剂的佐剂活性和副作用（局部炎症），我们得出结论，PLA微粒是H5N1流感裂解疫苗有前景的替代佐剂。
