Tyrosine-Based Cross-Linking of Peptide Antigens to Generate Nanoclusters with Enhanced Immunogenicity: Demonstration Using the Conserved M2e Peptide of Influenza A.
Tyrosine-Based Cross-Linking of Peptide Antigens to Generate Nanoclusters with Enhanced Immunogenicity: Demonstration Using the Conserved M2e Peptide of Influenza A.
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DOI：
10.1021/acsinfecdis.1c00219
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发表时间：
2021-09-10
影响因子：
5.3
通讯作者：
Gill HS
中科院分区：
文献类型：
--
作者：
Wilks LR;Joshi G;Grisham MR;Gill HS
描述了一种利用基于酪氨酸-酪氨酸交联反应的方法从可溶性肽分子产生纳米簇（NC）的方法。在肽分子的末端引入包含组氨酸和酪氨酸残基的反应性标签。交联反应导致在标签内产生双酪氨酸键，这允许产生肽NC。我们表明，它是必不可少的反应性标签存在于两个'N'和'C'端的肽簇形成发生。此外，交联反应进行了系统的表征，以显示反应条件对最终簇直径的重要性，使我们能够生成各种尺寸的NC。为了证明肽簇的免疫原性潜力，我们选择研究保守的流感肽M2 e作为抗原。使用交联反应配制M2 e NC。我们显示了簇在BALB/c小鼠中以剂量、大小和频率依赖性方式产生针对致死性甲型流感挑战的保护性免疫的能力。总之，所呈现的数据表明这种新的簇形成技术可以以简单和可控的方式产生高度免疫原性的肽NC。
A method of creating nanoclusters (NCs) from soluble peptide molecules is described utilizing an approach based on a tyrosine-tyrosine crosslinking reaction. A reactive tag comprising histidine and tyrosine residues was introduced at the termini of the peptide molecules. The crosslinking reaction led to the creation of dityrosine bonds within the tag, which allowed for the generation of peptide NCs. We show that it is essential for the reactive tag to be present at both the ‘N’ and ‘C’ termini of the peptide for cluster formation to occur. Additionally, the crosslinking reaction was systematically characterized to show the importance of reaction conditions on final cluster diameter, allowing us to generate NCs of various sizes. To demonstrate the immunogenic potential of the peptide clusters, we chose to study the conserved influenza peptide, M2e, as the antigen. M2e NCs were formulated using the crosslinking reaction. We show the ability of the clusters to generate protective immunity in a dose, size, and frequency dependent manner against a lethal influenza A challenge in BALB/c mice. Taken together, the data presented suggests this new cluster formation technique can generate highly immunogenic peptide NCs in a simple and controllable manner.
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影响因子：
6.2
作者：
Bode C;Zhao G;Steinhagen F;Kinjo T;Klinman DM
通讯作者：
Klinman DM
影响因子：
9.8
作者：
Arnesen T
通讯作者：
Arnesen T
影响因子：
4.1
作者：
Gill, G;RichterRusli, AA;Rokita, SE
通讯作者：
Rokita, SE
影响因子：
3
作者：
Banerjee, Kaushik;Biswas, Manas Kumar;Choudhuri, Soumitra Kumar
通讯作者：
Choudhuri, Soumitra Kumar
影响因子：
4
作者：
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通讯作者：
Draper SJ