Vaccine delivery by zwitterionic polysaccharide-based hydrogel microparticles showing enhanced immunogenicity and suppressed foreign body responses,Biomaterials Science

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Vaccine delivery by zwitterionic polysaccharide-based hydrogel microparticles showing enhanced immunogenicity and suppressed foreign body responses
Biomaterials Science ( IF 5.8 ) Pub Date : 2023-06-09 , DOI: 10.1039/d2bm01960d
Jin Teng Chung ₁ , Chi Ming Laurence Lau ₁ , Casper H Y Chung ₂ , Mehrnoosh Rafiei _{1,

3} , Shuhuai Yao ₂ , Ying Chau ₁

Affiliation

The controlled release of antigens from injectable depots has been actively pursued to achieve long-lasting immune responses in vaccine development. Nonetheless, subcutaneous depots are often susceptible to foreign body responses (FBRs) dominated by macrophage clearance and fibrotic encapsulation, resulting in limited antigen delivery to target dendritic cells (DCs) that bridge innate and adaptive immunity. Here, we aim to develop a long-term antigen depot that can bypass FBR and engage DCs to mature and migrate to lymph nodes to activate antigen-specific T-cells. Leveraging the immunomodulatory properties of exogenous polysaccharides and the anti-fouling characteristics of zwitterionic phosphorylcholine (PC) polymers, we developed a PC functionalized dextran (PCDX) hydrogel for long-term antigen delivery. We observed that PCDX in both injectable scaffold and microparticle (MP) forms could effectively evade FBR as the anionic carboxymethyl DX (CMDX) in vitro and in vivo. Meanwhile, PCDX provided slower and longer release of antigens than CMDX, resulting in local enrichment of CD11c+ DCs at the MP injection sites. DC cultured on PCDX exhibited stronger immunogenic activation with higher CD86, CD40, and MHC-I/peptide complex than CMDX. PCDX also generated DC with greater propensity in migration to lymph nodes, as well as antigen presentations to trigger both CD4+ and CD8+ arms of T-cell responses, as compared to other charge derivatives of DX. Besides cellular responses, PCDX could also induce more durable and potent humoral responses, with higher levels of antigen specific IgG1 and IgG2a by day 28, as compared to other treatment groups. In conclusion, PCDX can incorporate the benefits of both immunogenic DX and anti-fouling properties of zwitterionic PC and thus, shows great promise in providing long-term delivery of antigens for vaccine development.

中文翻译：

通过基于两性离子多糖的水凝胶微粒递送疫苗，显示出增强的免疫原性和抑制的异物反应

人们一直在积极寻求从注射剂库中控制抗原的释放，以在疫苗开发中实现持久的免疫反应。尽管如此，皮下储库通常容易受到以巨噬细胞清除和纤维化包膜为主的异物反应（FBR）的影响，导致向连接先天免疫和适应性免疫的目标树突细胞（DC）的抗原递送有限。在这里，我们的目标是开发一种长期抗原库，可以绕过 FBR 并使 DC 成熟并迁移到淋巴结以激活抗原特异性 T 细胞。利用外源多糖的免疫调节特性和两性离子磷酸胆碱（PC）聚合物的防污特性，我们开发了一种用于长期抗原递送的PC功能化葡聚糖（PCDX）水凝胶。体外和体内。同时，PCDX 比 CMDX 提供更慢、更长的抗原释放，导致 MP 注射位点局部富集 CD11c+ DC。与 CMDX 相比，在 PCDX 上培养的 DC 表现出更强的免疫原性激活，具有更高的 CD86、CD40 和 MHC-I/肽复合物。与 DX 的其他电荷衍生物相比，PCDX 还产生更倾向于迁移至淋巴结的 DC，以及触发 T 细胞反应的 CD4+ 和 CD8+ 臂的抗原呈递。除了细胞反应外，与其他治疗组相比，PCDX 还可以诱导更持久、更有效的体液反应，到第 28 天时抗原特异性 IgG1 和 IgG2a 水平更高。总之，PCDX 可以结合免疫原性 DX 的优点和两性离子 PC 的防污特性，因此，

更新日期：2023-06-09

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