工程合成DNA疫苗诱导对尼帕病毒的免疫应答

IF 2 Q4 VIROLOGY
Hyeree Choi, S. Kudchodkar, Ziyang Xu, Michelle Ho, Peng Xiao, S. Ramos, Laurent Humeau, D. Weiner, K. Muthumani
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摘要

尼帕病毒(NiV)是一种重新出现的病原体,可导致动物和人类的严重疾病。目前针对新冠病毒感染的治疗措施不足,也没有批准用于人类或动物的新冠病毒疫苗。尼帕病毒被世界卫生组织(世界卫生组织)列为疫苗和治疗研究的高度优先病原体。在本研究中,我们采用了合成增强DNA技术来设计和生产新的一致性NiV融合(NiV-F)和糖蛋白(NiV-G)抗原序列,用于包含在合成的NiV DNA疫苗中。使用免疫结合测定法在体外确认每种疫苗抗原的表达。电穿孔增强肌肉注射每种NiV-F和NiV-G到小鼠中诱导对NiV-G和NiV-F的多个表位的有效细胞免疫反应,所述表位包括抗原特异性CD8+T细胞。两种疫苗都在小鼠中引发了高抗体滴度,单次免疫足以使100%的免疫动物血清转化。此外,新冠肺炎疫苗还诱导抗体中和新冠肺炎假型病毒颗粒。这些数据支持进一步研究这些新的合成增强的基于NiV核酸的抗原,作为针对Nipah病毒的有效疫苗的潜在成分。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Elicitation of immune responses against Nipah virus by an engineered synthetic DNA vaccine
Nipah virus (NiV) is a re-emerging pathogen that causes severe disease in animals and humans. Current treatment measures for NiV infection are insufficient, and there is no approved vaccine against NiV for either humans or animals. Nipah virus is listed as a high-priority pathogen for vaccine and therapeutic research by the World Health Organization (WHO). In the present study, we employed synthetic enhanced DNA technologies developed to design and produce novel consensus NiV Fusion (NiV-F) and Glycoprotein (NiV-G) antigen sequences for inclusion in synthetic DNA vaccines for NiV. The expression of each vaccine antigen was confirmed in vitro using immune-binding assays. Electroporation-enhanced intramuscular injection of each NiV-F and NiV-G into mice induced potent cellular immune responses to multiple epitopes of NiV-G and NiV-F that included antigen-specific CD8+ T cells. Both vaccines elicited high antibody titers in mice, with a single immunization sufficient to seroconvert 100% of immunized animals. Additionally, the NiV-F vaccine also induced antibodies to neutralize NiV-F-pseudotyped virus particles. These data support further study of these novel synthetic enhanced NiV nucleic acid-based antigens as potential components of an effective vaccine against the Nipah virus.
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