Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses.
Glycan-Modified Virus-like Particles Evoke T Helper Type 1-like Immune Responses.
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DOI：
10.1021/acsnano.0c03023
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发表时间：
2021-01-26
期刊：
影响因子：
17.1
通讯作者：
Kiessling LL
中科院分区：
文献类型：
--
作者：
Alam MM;Jarvis CM;Hincapie R;McKay CS;Schimer J;Sanhueza CA;Xu K;Diehl RC;Finn MG;Kiessling LL
树突状细胞（Dendritic cells，DC）是一种高效的抗原提呈细胞。将抗原递送到DC的疫苗可以利用它们的力量。DC表面凝集素识别通常不存在于宿主组织上的聚糖，以促进抗原摄取和呈递。靶向这些表面凝集素的疫苗应该提供改进的抗原递送，但它们的功效将取决于凝集素靶向如何影响产生的T细胞亚型。我们研究了抗原结构如何影响C型凝集素DC-SIGN（树突状细胞特异性细胞间粘附分子-3-抓取非整合素，CD 209）的摄取和信号传导。病毒样纳米颗粒（VLP）由噬菌体Qβ工程化以呈递甘露糖苷配体阵列。VLP被DC摄取并有效地运输到内体。随后的信号传导依赖于VLP上展示的配体：只有那些用芳基甘露糖苷Qβ-Man 540密集功能化的颗粒才能引发DC成熟并诱导促炎细胞因子的表达，这些促炎细胞因子是T辅助细胞1型（TH 1）样免疫应答的特征。这种效应可追溯到在内体的酸性pH下与DC-SIGN的差异结合。用带有芳基甘露糖苷的VLP和肽抗原（Qβ-Ova-Man 540）免疫小鼠，具有抗原特异性应答，包括产生活化细胞因子干扰素-γ和肿瘤坏死因子-α的CD 4 + T细胞的产生。TH 1应答对于细胞内病原体（例如，病毒）和癌症;因此，我们的数据突出了靶向DC凝集素用于抗原递送的价值，并验证了靶向DC的VLP作为诱导细胞免疫的疫苗载体的效用。
Dendritic cells (DCs) are highly effective antigen-presenting cells that shape immune responses. Vaccines that deliver antigen to the DCs can harness their power. DC surface lectins recognize glycans not typically present on host tissue to facilitate antigen uptake and presentation. Vaccines that target these surface lectins should offer improved antigen delivery, but their efficacy will depend on how lectin targeting influences the T cell subtypes that result. We examined how antigen structure influences uptake and signaling from the C-type lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin, CD209). Virus-like nanoparticles (VLPs) were engineered from bacteriophage Qβ to present an array of mannoside ligands. The VLPs were taken up by DCs and efficiently trafficked to endosomes. The signaling that ensued depended on the ligand displayed on the VLP: only those particles densely functionalized with an aryl mannoside, Qβ-Man540, elicited DC maturation and induced the expression of the proinflammatory cytokines characteristic of a T helper type 1 (TH1)-like immune response. This effect was traced to differential binding to DC-SIGN at the acidic pH of the endosome. Mice were immunized with a VLP bearing the aryl mannoside and a peptide antigen (Qβ-Ova-Man540) had antigen-specific responses, including the production of CD4+ T cells producing the activating cytokines interferon-γ and tumor necrosis factor-α. A TH1 response is critical for intracellular pathogens (e.g., viruses) and cancer; thus, our data highlight the value of targeting DC lectins for antigen delivery and validate the utility of DC-targeted VLPs as vaccine vehicles that induce cellular immunity.
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影响因子：
64.5
作者：
Geijtenbeek, TBH;Torensma, R;Figdor, CG
通讯作者：
Figdor, CG
疫苗开发中的大肠杆菌衍生病毒样颗粒
影响因子：
9.2
作者：
Huang X;Wang X;Zhang J;Xia N;Zhao Q
通讯作者：
Zhao Q
影响因子：
64.5
作者：
Chevrier N;Mertins P;Artyomov MN;Shalek AK;Iannacone M;Ciaccio MF;Gat-Viks I;Tonti E;DeGrace MM;Clauser KR;Garber M;Eisenhaure TM;Yosef N;Robinson J;Sutton A;Andersen MS;Root DE;von Andrian U;Jones RB;Park H;Carr SA;Regev A;Amit I;Hacohen N
通讯作者：
Hacohen N
影响因子：
3.7
作者：
Al-Barwani F;Young SL;Baird MA;Larsen DS;Ward VK
通讯作者：
Ward VK
影响因子：
15
作者：
Hudson KL;Bartlett GJ;Diehl RC;Agirre J;Gallagher T;Kiessling LL;Woolfson DN
通讯作者：
Woolfson DN