靶向β冠状病毒刺突蛋白的DNA疫苗通过双重抗病毒免疫调节作用阻断猪的神经侵袭和神经炎症。

DNA vaccine targeting betacoronavirus spike protein blocks neuroinvasion and neuroinflammation in swine via dual antiviral-immunomodulatory action.

作者信息

Yu Huabo, Shi Junchao, Fu Guoce, Cao Zezhao, Qiu Ruizhao, Zhao Tianqi, Zhang Jing, Lan Yungang, Guan Jiyu, Zhao Kui, Gao Feng, He Wenqi, Li Zi

机构信息

State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.

出版信息

NPJ Vaccines. 2025 Aug 7;10(1):187. doi: 10.1038/s41541-025-01247-1.

DOI:10.1038/s41541-025-01247-1

PMID:40774966

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12331951/

Abstract

Porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus, causes fatal neurological disease in piglets, yet no licensed vaccines exist. Here, we developed a DNA vaccine encoding the receptor-binding domain (RBD) of PHEV spike protein fused to IgG1 Fc, adjuvanted with GEL01 (RBD + GEL01). Immunization in mice and piglets elicited robust neutralizing antibodies (titers up to 1:446 and 1:147, respectively) and Th1-biased cellular immunity. The vaccine restricted viral neuroinvasion, reducing brain viral loads by >90% and confining PHEV to discrete olfactory and cortical regions. Vaccinated animals exhibited preserved motor coordination, cognitive function, and minimal neuropathology. Transcriptomic analysis revealed suppression of proinflammatory mediators (e.g., Cxcl2, Saa3) and enhanced neural repair pathways, highlighting dual virological control and immunomodulatory mechanisms. As the first DNA vaccine against PHEV, the RBD + GEL01 candidate offers scalable protection against neurotropic coronaviruses by dual antiviral-immunomodulatory strategy, underscoring its potential to mitigate economic and zoonotic risks.

摘要

猪血凝性脑脊髓炎病毒（PHEV）是一种嗜神经性β冠状病毒，可导致仔猪患上致命的神经疾病，但目前尚无获批的疫苗。在此，我们研发了一种DNA疫苗，其编码与IgG1 Fc融合的PHEV刺突蛋白受体结合域（RBD），并佐以GEL01（RBD + GEL01）。对小鼠和仔猪进行免疫接种后，引发了强大的中和抗体（效价分别高达1:446和1:147）以及以Th1为主导的细胞免疫。该疫苗限制了病毒的神经侵袭，使脑内病毒载量降低了90%以上，并将PHEV局限于离散的嗅觉和皮质区域。接种疫苗的动物表现出运动协调和认知功能得以保留，且神经病理学变化轻微。转录组分析显示促炎介质（如Cxcl2、Saa3）受到抑制，神经修复途径增强，突出了双重病毒学控制和免疫调节机制。作为首个针对PHEV的DNA疫苗，RBD + GEL01候选疫苗通过双重抗病毒免疫调节策略提供了针对嗜神经性冠状病毒的可扩展保护，强调了其减轻经济和人畜共患病风险的潜力。