Co-Anchoring of Engineered Immunogen and Immunostimulatory Cytokines to Alum Promotes Enhanced-Humoral Immunity.
Co-Anchoring of Engineered Immunogen and Immunostimulatory Cytokines to Alum Promotes Enhanced-Humoral Immunity.
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工程免疫原和免疫刺激细胞因子共同锚定在明矾上促进增强的体液免疫。
DOI：
10.1002/adtp.202100235
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发表时间：
2022-07
影响因子：
4.6
通讯作者：
Irvine, Darrell J.
中科院分区：
文献类型：
--
作者：
Chang, Jason Y. H.;Agarwal, Yash;Rodrigues, Kristen A.;Momin, Noor;Ni, Kaiyuan;Read, Benjamin J.;Moyer, Tyson J.;Mehta, Naveen K.;Silva, Murillo;Suh, Heikyung;Melo, Mariane B.;Wittrup, K. Dane;Irvine, Darrell J.
蛋白质抗原通常与氢氧化铝（明矾）组合，氢氧化铝是许可疫苗中最常用的佐剂;但明矾佐剂疫苗的免疫原性仍有很大的改进空间。在这里，作者展示了一种免疫刺激性细胞因子白细胞介素IL-21与工程化外域（eOD）人类免疫缺陷病毒gp 120 Env免疫原eOD共同递送的策略，这些免疫刺激性细胞因子与明矾结合在一起以增强体液免疫应答。在这种方法中，免疫原和细胞因子通过短磷酸丝氨酸（pSer）肽接头共同锚定在明矾颗粒上，促进与明矾的稳定结合和注射后的持续生物利用度。pSer修饰的eOD和IL-21促进淋巴引流增强，并导致疫苗在引流淋巴结的B细胞滤泡中蓄积。这反过来又促进了增强的T滤泡辅助细胞引发和稳健的生发中心反应以及增加的抗原特异性血清IgG滴度。这是免疫刺激性细胞因子与免疫原共递送的一般策略，提供了使用最常见的临床疫苗佐剂调节T细胞引发和GC反应以增强保护性免疫的简易方法。明矾是临床上最常见的疫苗佐剂，然而，当与亚单位蛋白抗原结合时，明矾常常激发弱的免疫应答。在这里，作者开发了一种通过将疫苗抗原和细胞因子白细胞介素-21（IL-21）共同锚定到明矾颗粒来增强免疫反应的策略; IL-21作为分子佐剂来增强针对抗原的抗体反应。
Protein antigens are often combined with aluminum hydroxide (alum), the most commonly used adjuvant in licensed vaccines; yet the immunogenicity of alum‐adjuvanted vaccines leaves much room for improvement. Here, the authors demonstrate a strategy for codelivering an immunostimulatory cytokine, the interleukin IL‐21, with an engineered outer domain (eOD) human immunodeficiency virus gp120 Env immunogen eOD, bound together to alum to bolster the humoral immune response. In this approach, the immunogen and cytokine are co‐anchored to alum particles via a short phosphoserine (pSer) peptide linker, promoting stable binding to alum and sustained bioavailability following injection. pSer‐modified eOD and IL‐21 promote enhanced lymphatic drainage and lead to accumulation of the vaccine in B cell follicles in the draining lymph nodes. This in turn promotes enhanced T follicular helper cell priming and robust germinal center responses as well as increased antigen‐specific serum IgG titers. This is a general strategy for codelivery of immunostimulatory cytokine with immunogens providing a facile approach to modulate T cell priming and GC reactions toward enhanced protective immunity using the most common clinical vaccine adjuvant. Alum is the most common clinical vaccine adjuvant; however, alum often elicits weak immune responses when combined with subunit protein antigens. Here, the authors develop a strategy to boost the immune response by co‐anchoring vaccine antigens and the cytokine interleukin‐21 (IL‐21) to alum particles; IL‐21 acts as a molecular adjuvant to enhance the antibody response against the antigen.
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影响因子：
7.3
作者：
Moens L;Tangye SG
通讯作者：
Tangye SG
影响因子：
32.4
作者：
Nurieva, Roza I.;Chung, Yeonseok;Hwang, Daehee;Yang, Xuexian O.;Kang, Hong Soon;Ma, Li;Wang, Yi-Hong;Watowich, Stephanie S.;Jetten, Anton M.;Tian, Qiang;Dong, Chen
通讯作者：
Dong, Chen
影响因子：
28.1
作者：
通讯作者：
--
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
7
作者：
Cirelli KM;Crotty S
通讯作者：
Crotty S