Multidomain peptide hydrogel adjuvants elicit strong bias towards humoral immunity.
Multidomain peptide hydrogel adjuvants elicit strong bias towards humoral immunity.
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DOI：
10.1039/d2bm01242a
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发表时间：
2022-10-25
影响因子：
6.6
通讯作者：
McHugh, Kevin J.
中科院分区：
文献类型：
--
作者：
Pogostin, Brett H.;Yu, Marina H.;Azares, Alon R.;Euliano, Erin M.;Lai, Cheuk Sun Edwin;Saenz, Gabriel;Wu, Samuel X.;Farsheed, Adam C.;Melhorn, Sarah M.;Graf, Tyler P.;Woodside, Darren G.;Hartgerink, Jeffrey D.;McHugh, Kevin J.
佐剂在增强疫苗功效方面发挥着关键作用；然而，需要开发新的免疫调节化合物来应对新出现的病原体并扩大免疫疗法的使用。多域肽（MDP）是由经典氨基酸组成的材料，在生理盐和 pH 条件下形成可注射的超分子水凝胶。 MDP 水凝胶在体内被免疫细胞快速渗透，并且之前已被证明可以影响细胞因子的产生。因此，我们假设这些免疫刺激特性将使 MDP 能够充当疫苗佐剂。在此，我们证明将抗原加载到 MDP 水凝胶中不会干扰其流变特性，并且带正电荷的 MDP 可以充当抗原库，正如它们在体内 7-9 天释放卵清蛋白 (OVA) 的能力所证明的那样。接种 MDP 佐剂抗原的小鼠产生的 IgG 滴度明显高于未加佐剂对照的小鼠，表明这些水凝胶增强了体液免疫。有趣的是，与接种明矾佐剂 OVA 的小鼠相比，MDP 水凝胶并没有引发强大的细胞免疫反应，IgG2c 的产生量较低，四聚体阳性 CD8+ T 脾细胞数量也较少。总之，数据表明 MDP 水凝胶佐剂使免疫反应强烈偏向于体液免疫，同时引起非常有限的细胞免疫反应。因此，MDP 可能有潜力作为佐剂用于仅受益于体液免疫的应用。
Adjuvants play a critical role in enhancing vaccine efficacy; however, there is a need to develop new immunomodulatory compounds to address emerging pathogens and to expand the use of immunotherapies. Multidomain peptides (MDPs) are materials composed of canonical amino acids that form injectable supramolecular hydrogels under physiological salt and pH conditions. MDP hydrogels are rapidly infiltrated by immune cells in vivo and have previously been shown to influence cytokine production. Therefore, we hypothesized that these immunostimulatory characteristics would allow MDPs to function as vaccine adjuvants. Herein, we demonstrate that loading antigen into MDP hydrogels does not interfere with their rheological properties and that positively charged MDPs can act as antigen depots, as demonstrated by their ability to release ovalbumin (OVA) over a period of 7-9 days in vivo. Mice vaccinated with MDP-adjuvanted antigen generated significantly higher IgG titers than mice treated with the unadjuvanted control, suggesting that these hydrogels potentiate humoral immunity. Interestingly, MDP hydrogels did not elicit a robust cellular immune response, as indicated by the lower production of IgG2c and smaller populations of tetramer-positive CD8+ T splenocytes compared to mice vaccinated alum-adjuvanted OVA. Together, the data suggest that MDP hydrogel adjuvants strongly bias the immune response towards humoral immunity while evoking a very limited cellular immune response. As a result, MDPs may have the potential to serve as adjuvants for applications that benefit exclusively from humoral immunity.
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