Self-Assembly of Immune Signals to Program Innate Immunity through Rational Adjuvant Design.
Self-Assembly of Immune Signals to Program Innate Immunity through Rational Adjuvant Design.
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DOI：
10.1002/advs.202202393
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发表时间：
2022-11-14
期刊：
影响因子：
15.1
通讯作者：
Jewell, Christopher M.
中科院分区：
文献类型：
--
作者：
Bookstaver, Michelle L.;Zeng, Qin;Oakes, Robert S.;Kapnick, Senta M.;Saxena, Vikas;Edwards, Camilla;Venkataraman, Nishedhya;Black, Sheneil K.;Zeng, Xiangbin;Froimchuk, Eugene;Gebhardt, Thomas;Bromberg, Jonathan S.;Jewell, Christopher M.
最近的临床研究表明，激活多种先天免疫途径可驱动感染和癌症的强烈反应。生物材料提供了输送多种货物的有用功能，但增加了翻译复杂性和内在免疫特征，使合理设计变得复杂。这里使用自组装创建了一个模块化佐剂平台，以构建完全由抗原和多种 Toll 样受体激动剂 (TLRas) 组成的纳米结构胶囊。这些组件将 TLR 隔离到内溶酶体中，从而可以对通过这些受体转导的相对信号传导水平进行可编程控制。引人注目的是，这种先天信号传导的组合控制可以针对特定抗原产生不同的抗原特异性反应。这些组装体驱动淋巴结基质重组至亲免疫微环境，从而扩大抗原特异性 T 细胞。令人兴奋的是，与具有单个 TLRa 的混合制剂或胶囊相比，由抗原和多个 TLRas 构建的组件增强了 T 细胞功能和抗肿瘤功效。最后，由临床相关的人类黑色素瘤抗原和多达三个 TLRa 类别构建的胶囊能够同时控制每个途径的信号转导。这创建了一个简便的佐剂设计平台，可以在不使用载体成分的情况下定制疫苗和免疫疗法的信号传导。模块化特性支持抗原与与几个先天受体家族相关的激动剂的精确并置，例如 Toll、STING、NOD 和 RIG。肽抗原和 Toll 样受体激动剂的不同组合和比例自组装成免疫聚电解质多层揭示了激活多个 Toll 样受体信号通路产生不同类型的抗原特异性反应。该策略可用于通过针对单一抗原发起多方面的免疫攻击来改进疫苗设计，从而产生强大的抗原特异性免疫。
Recent clinical studies show activating multiple innate immune pathways drives robust responses in infection and cancer. Biomaterials offer useful features to deliver multiple cargos, but add translational complexity and intrinsic immune signatures that complicate rational design. Here a modular adjuvant platform is created using self‐assembly to build nanostructured capsules comprised entirely of antigens and multiple classes of toll‐like receptor agonists (TLRas). These assemblies sequester TLR to endolysosomes, allowing programmable control over the relative signaling levels transduced through these receptors. Strikingly, this combinatorial control of innate signaling can generate divergent antigen‐specific responses against a particular antigen. These assemblies drive reorganization of lymph node stroma to a pro‐immune microenvironment, expanding antigen‐specific T cells. Excitingly, assemblies built from antigen and multiple TLRas enhance T cell function and antitumor efficacy compared to ad‐mixed formulations or capsules with a single TLRa. Finally, capsules built from a clinically relevant human melanoma antigen and up to three TLRa classes enable simultaneous control of signal transduction across each pathway. This creates a facile adjuvant design platform to tailor signaling for vaccines and immunotherapies without using carrier components. The modular nature supports precision juxtaposition of antigen with agonists relevant for several innate receptor families, such as toll, STING, NOD, and RIG. Self‐assembly of peptide antigen and distinct combinations and ratios of toll‐like receptor agonists into immune polyelectrolyte multilayers reveal activating multiple toll‐like receptor signaling pathways generates distinct types of antigen‐specific response. This strategy can be used to improve vaccine design by initiating a multifaceted immune attack against a singular antigen creating robust antigen‐specific immunity.
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影响因子：
5.4
作者：
Goldinger, Simone M.;Dummer, Reinhard;Baumgaertner, Petra;Mihic-Probst, Daniela;Schwarz, Katrin;Hammann-Haenni, Anya;Willers, Joerg;Geldhof, Christine;Prior, John O.;Kuendig, Thomas M.;Michielin, Olivier;Bachmann, Martin F.;Speiser, Daniel E.
通讯作者：
Speiser, Daniel E.
影响因子：
3.6
作者：
Diehl, S;Rincón, M
通讯作者：
Rincón, M
影响因子：
38.3
作者：
Faria M;Björnmalm M;Thurecht KJ;Kent SJ;Parton RG;Kavallaris M;Johnston APR;Gooding JJ;Corrie SR;Boyd BJ;Thordarson P;Whittaker AK;Stevens MM;Prestidge CA;Porter CJH;Parak WJ;Davis TP;Crampin EJ;Caruso F
通讯作者：
Caruso F
影响因子：
82.9
作者：
Gattinoni L;Speiser DE;Lichterfeld M;Bonini C
通讯作者：
Bonini C
影响因子：
17.1
作者：
Dhodapkar MV;Sznol M;Zhao B;Wang D;Carvajal RD;Keohan ML;Chuang E;Sanborn RE;Lutzky J;Powderly J;Kluger H;Tejwani S;Green J;Ramakrishna V;Crocker A;Vitale L;Yellin M;Davis T;Keler T
通讯作者：
Keler T