PDF(Pubmed)
Abstract：
Respiratory syncytial virus (RSV) is a serious human respiratory pathogen that commonly affects children, older adults, and immunocompromised individuals. At present, the design of licensed vaccines focuses on the incorporation of the pre-fusion protein (PreF protein) of RSV, as this protein has the ability to induce antibodies that offer a high level of protection. Moreover, the G protein contains the CX3C motif that binds the chemokine receptor CX3CR1 in respiratory epithelial cells, which plays an essential role in viral infection. Therefore, incorporating the G antigen into vaccine design may prove more advantageous for RSV prevention. In this study, we developed a human adenoviral vector-based RSV vaccine containing highly neutralizing immunogens, a modified full-length PreF protein fused with the central conserved peptides of the G protein (Gcc) from both RSV subgroups trimerized via a C-terminal foldon, and evaluated its immune response in mice through intranasal (i.n.) immunization. Our results showed that immunization with Ad5-PreF-Qa-Gcc elicited a balanced Th1/Th2 immune response and robust mucosal immunity with higher neutralizing antibody titers against RSV Long and RSV B1. Importantly, immunization with Ad5-PreF-Qa-Gcc enhanced CD4+ CD25+ FoxP3+ Treg cell response and protected the mice against RSV infection. Our data demonstrate that the combination of Gcc and the PreF antigen is a viable strategy for developing effective RSV vaccines.
摘要：
呼吸道合胞病毒（RSV）是一种严重的人类呼吸道病原体，通常会影响儿童，老年人,和免疫受损的个体。目前,许可疫苗的设计侧重于RSV的预融合蛋白（PreF蛋白）的掺入，因为这种蛋白质具有诱导提供高水平保护的抗体的能力。此外，G蛋白含有与呼吸道上皮细胞中趋化因子受体CX3CR1结合的CX3C基序，在病毒感染中起着至关重要的作用。因此,将G抗原掺入疫苗设计中可能证明对RSV预防更有利。在这项研究中,我们开发了一种基于人腺病毒载体的RSV疫苗，含有高中和免疫原，与来自两个RSV亚组的G蛋白（Gcc）的中央保守肽融合的修饰的全长PreF蛋白通过C末端折叠三聚，并通过鼻内（i.n.）免疫评估其在小鼠中的免疫应答。我们的结果表明，用Ad5-PreF-Qa-Gcc免疫可引起平衡的Th1/Th2免疫应答和强大的粘膜免疫，具有较高的针对RSVLong和RSVB1的中和抗体滴度。重要的是,用Ad5-PreF-Qa-Gcc免疫增强CD4+CD25+FoxP3+Treg细胞应答并保护小鼠免受RSV感染。我们的数据表明Gcc和PreF抗原的组合是开发有效RSV疫苗的可行策略。
