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评估一种基于 mRNA 的尼帕病毒候选疫苗在猪中的免疫原性。

Evaluation of the immunogenicity of an mRNA vectored Nipah virus vaccine candidate in pigs.

机构信息

The Pirbright Institute, Pirbright, United Kingdom.

Australian Centre for Disease Preparedness, Geelong, VIC, Australia.

出版信息

Front Immunol. 2024 Apr 25;15:1384417. doi: 10.3389/fimmu.2024.1384417. eCollection 2024.

Abstract

Nipah virus (NiV) poses a significant threat to human and livestock populations across South and Southeast Asia. Vaccines are required to reduce the risk and impact of spillover infection events. Pigs can act as an intermediate amplifying host for NiV and, separately, provide a preclinical model for evaluating human vaccine candidate immunogenicity. The aim of this study was therefore to evaluate the immunogenicity of an mRNA vectored NiV vaccine candidate in pigs. Pigs were immunized twice with 100 μg nucleoside-modified mRNA vaccine encoding soluble G glycoprotein from the Malaysia strain of NiV, formulated in lipid nanoparticles. Potent antigen-binding and virus neutralizing antibodies were detected in serum following the booster immunization. Antibody responses effectively neutralized both the Malaysia and Bangladesh strains of NiV but showed limited neutralization of the related (about 80% amino acid sequence identity for G) Hendra virus. Antibodies were also capable of neutralizing NiV glycoprotein mediated cell-cell fusion. NiV G-specific T cell cytokine responses were also measurable following the booster immunization with evidence for induction of both CD4 and CD8 T cell responses. These data support the further evaluation of mRNA vectored NiV G as a vaccine for both pigs and humans.

摘要

尼帕病毒(NiV)对南亚和东南亚的人类和牲畜构成重大威胁。需要疫苗来降低溢出感染事件的风险和影响。猪可以作为 NiV 的中间扩增宿主,并且可以单独作为评估人类疫苗候选物免疫原性的临床前模型。因此,本研究旨在评估一种基于 mRNA 的 NiV 疫苗候选物在猪中的免疫原性。猪用脂质纳米粒包封的编码来自马来西亚 NiV 株的可溶性 G 糖蛋白的 100μg 核苷修饰 mRNA 疫苗进行两次免疫。在加强免疫后,血清中检测到有效的抗原结合和病毒中和抗体。抗体反应有效地中和了马来西亚和孟加拉国的 NiV 株,但对相关的亨德拉病毒(约 80%的 G 氨基酸序列同一性)显示出有限的中和作用。抗体还能够中和 NiV 糖蛋白介导的细胞-细胞融合。加强免疫后,也可以测量 NiV G 特异性 T 细胞细胞因子反应,表明诱导了 CD4 和 CD8 T 细胞反应。这些数据支持进一步评估基于 mRNA 的 NiV G 作为猪和人类的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f282/11079202/e52a677373cd/fimmu-15-1384417-g001.jpg

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