Peptide Cross-Linking Using Tyrosine Residues Facilitated by an Exogenous Nickel-Histidine Complex: A Facile Approach for Enhancing Vaccine-Specific Immunogenicity.
Peptide Cross-Linking Using Tyrosine Residues Facilitated by an Exogenous Nickel-Histidine Complex: A Facile Approach for Enhancing Vaccine-Specific Immunogenicity.
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利用外源镍-组氨酸复合物促进的酪氨酸残基进行肽交联：一种增强疫苗特异性免疫原性的简便方法。
DOI：
10.1021/acsinfecdis.2c00265
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发表时间：
2022
影响因子：
5.3
通讯作者：
Gill,HarvinderSingh
中科院分区：
文献类型：
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作者：
Wilks,LoganR;Joshi,Gaurav;Kang,Sang-Moo;Wang,Bao-Zhong;Gill,HarvinderSingh
描述了一种使用二酪氨酸交联产生肽疫苗的改进方法。通过在N-和C-末端添加小的富含酪氨酸的区域（GYGY-）来修饰甲型流感病毒的保守离子通道肽M2 e，并通过酪氨酸-酪氨酸键广泛交联以形成肽纳米簇。在氧化剂的存在下，使用与外源性甘氨酸-甘氨酸-组氨酸肽复合的外源性镍（II）离子催化交联。用M2 e疫苗纳米簇鼻内或肌内免疫的小鼠诱导相当水平的M2 e特异性血清抗体。通过鼻内或肌内途径接种保护小鼠免受随后的甲型流感病毒致死性攻击。与我们先前的方法相比，其中将富含组氨酸的标签添加到肽结构中，外源组氨酸的使用减少了不相关的脱靶免疫应答。此外，所得纳米团簇的纯度是一个有吸引力的特征，使得这种方法对疫苗开发有吸引力。
An improved method for the generation of peptide vaccines using di-tyrosine cross-linking is described. The conserved ion channel peptide, M2e, of influenza A virus was modified with the addition of small tyrosine-rich regions (GYGY-) at both the N- and C-termini and extensively cross-linked via tyrosine–tyrosine linkages to form peptide nanoclusters. The cross-linking was catalyzed using exogenous nickel(II) ions complexed to an exogenous glycine–glycine–histidine peptide in the presence of an oxidizer. Mice that were intranasally or intramuscularly immunized with the M2e-vaccine nanoclusters induced comparable levels of M2e-specific serum antibodies. Vaccination via the intranasal or intramuscular route protected mice from subsequent lethal challenge with an influenza A virus. In comparison to our previous approach, where a histidine-rich tag was added into the peptide structure, the use of exogenous histidine reduced irrelevant off-target immune response. Additionally, the purity of the resulting nanoclusters is an attractive feature, making this approach appealing for vaccine development.