A minimalist supramolecular nanovaccine forcefully propels the Tfh cell and GC B cell responses
A minimalist supramolecular nanovaccine forcefully propels the Tfh cell and GC B cell responses
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极简超分子纳米疫苗强力推动 Tfh 细胞和 GC B 细胞反应
DOI：
10.1016/j.cej.2022.134782
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发表时间：
2022-02-09
影响因子：
15.1
通讯作者：
Liu, Jianfeng
中科院分区：
文献类型：
--
作者：
Jia, Haixue;Shang, Yuna;Liu, Jianfeng
与包含灭活或减毒的完整病原体的疫苗相比，基于蛋白质抗原的亚单位疫苗更安全且更容易制造。然而，亚单位疫苗通常表现出弱且不持久的免疫反应，这主要是由于抗原呈递细胞对它们的摄取较差。为了解决这个问题，我们开发了一种氟化芳香肽（F-AP），其中氟的电负性是为了增强其与抗原的亲和力和跨膜能力。在小鼠模型中，F-AP 的抗体滴度分别比 AP 和传统铝佐剂高 4 倍和 501 倍。与抗体反应一致，F-AP极大地促进了滤泡辅助T细胞和成熟B细胞的增殖。有趣的是，接种 F-AP 疫苗后，淋巴结中的传统 1 型树突状细胞 (cDC1) 也有所增加。抗原定位实验表明，F-AP有助于抗原从细胞溶酶体中逃逸，这表明F AP可能通过cDC1′的抗原交叉呈递功能诱导细胞免疫反应。总的来说，数据表明，芳香肽 F-AP 上的简单氟基修饰可以改善亚基抗原的免疫反应。因此，氟化策略可能为纳米材料增强疫苗或免疫疗法的疫苗接种免疫反应提供一种新方法。
Compared with vaccines comprising inactivated or attenuated whole pathogens, the subunit vaccines based on protein antigens are safer and easier to manufacture. Yet subunit vaccines usually exhibit weak and nondurable immune responses, which is mainly due to their poor uptake by antigen-presenting cells. To address this issue, we develop a fluorinated aromatic peptide (F-AP), in which electronegativity of fluorine is to enhance its affinity with antigens and ability of transmembrane. In mice model, F-AP demonstrated over 4-fold and 501-fold higher antibody titers than AP and conventional aluminum adjuvant, respectively. Consistent with the antibody responses, F-AP greatly promoted the proliferation of T follicular helper cell and mature B cell. Intriguingly, conventional type 1 dendritic cells (cDC1) were also increased in lymph nodes with F-AP vaccination. And antigens localization experiments showed that F-AP help antigens escape from cell lysosomes, indicating that F AP could potentially induce cellular immune responses through cDC1 & PRIME;s antigen cross-presentation function. Collectively, the data suggest that simple fluorine group modification on aromatic peptide, F-AP, could improve the immune response of subunit antigens. Thus, fluoridation strategy may provide a novel approach for nano materials enhancing the vaccination immune response of vaccines or immunotherapies.