四基因缺失伪狂犬病毒ASFV抗原递送平台的构建与评价

IF 3 2区 农林科学 Q2 INFECTIOUS DISEASES
Hui Li, Ruhai Guo, Yanqing Jia, Xiao Zhang, Zishan Liu, WenLi Shi, Ruochen Hu, YiNing Zhang, Saba Nasir, Likang Han, Xinxin Qiu, Xinglong Wang
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引用次数: 0

摘要

非洲猪瘟(ASF)是一种高度致命的猪病毒性疾病。自2018年以来,非洲猪瘟病毒(ASFV)在中国的出现和快速传播给养猪业造成了重大经济损失。非洲猪瘟的复杂性阻碍了有效疫苗的开发,而且中国目前没有商业化疫苗,这凸显了对安全有效的候选疫苗的迫切需求。在本研究中,我们利用高免疫原性的四基因缺失重组伪狂犬病毒(rPRV SX-10ΔUL24/TK/gI/gE)为载体,利用HDR-CRISPR/Cas9系统构建了表达ASFV p54、p72、CD2v和pp62蛋白的重组病毒株。这些菌株rPRV-p54+p72和rPRV-CD2v+pp62表现出稳定的遗传特性,并能有效表达和传递异源蛋白,同时保持与其亲本菌株相似的生物学特性。安全性评价表明,这两种重组菌株在免疫小鼠和仔猪中表现出良好的安全性。此外,特异性抗体酶联免疫吸附试验(ELISA)、淋巴细胞增殖试验以及CD3+、CD4+和CD8+ T淋巴细胞分析证明,菌株诱导了强大的体液和细胞免疫应答。这些发现表明,rPRV-p54+p72和rPRV-CD2v+pp62是很有希望预防PRV和ASFV感染的二价疫苗候选物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Construction and Evaluation of Quadruple-Gene-Deleted Pseudorabies Virus Platforms for ASFV Antigen Delivery

Construction and Evaluation of Quadruple-Gene-Deleted Pseudorabies Virus Platforms for ASFV Antigen Delivery

African Swine Fever (ASF) is a highly lethal viral disease in swine. The emergence and rapid spread of African Swine Fever virus (ASFV) in China, since 2018 have caused significant economic losses to the pig farming industry. The complexity of ASFV has impeded the development of effective vaccines, and with no commercial vaccines currently available in China, highlighting the urgent need for safe and efficacious vaccine candidates. In this study, we utilized a highly immunogenic quadruple-gene-deleted recombinant pseudorabies virus (PRV) strain (rPRV SX-10ΔUL24/TK/gI/gE) as a vector to construct two recombinant viral strains expressing ASFV p54, p72, CD2v, and pp62 proteins using the HDR-CRISPR/Cas9 system. These strains, rPRV-p54+p72 and rPRV-CD2v+pp62, demonstrated stable genetic characteristics and efficiently expressed and delivered heterologous proteins while maintaining biological properties similar to their parental strain. Safety evaluation revealed that both recombinant strains exhibited favorable safety profiles in immunized mice and piglets. Furthermore, the strains induced robust humoral and cellular immune responses, as evidenced by specific antibody enzyme-linked immunosorbent assay (ELISA), lymphocyte proliferation assays, and analysis of CD3+, CD4+, and CD8+ T lymphocytes. These findings suggest that rPRV-p54+p72 and rPRV-CD2v+pp62 are promising bivalent vaccine candidates for protecting against both PRV and ASFV infections.

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来源期刊
Transboundary and Emerging Diseases
Transboundary and Emerging Diseases 农林科学-传染病学
CiteScore
8.90
自引率
9.30%
发文量
350
审稿时长
1 months
期刊介绍: Transboundary and Emerging Diseases brings together in one place the latest research on infectious diseases considered to hold the greatest economic threat to animals and humans worldwide. The journal provides a venue for global research on their diagnosis, prevention and management, and for papers on public health, pathogenesis, epidemiology, statistical modeling, diagnostics, biosecurity issues, genomics, vaccine development and rapid communication of new outbreaks. Papers should include timely research approaches using state-of-the-art technologies. The editors encourage papers adopting a science-based approach on socio-economic and environmental factors influencing the management of the bio-security threat posed by these diseases, including risk analysis and disease spread modeling. Preference will be given to communications focusing on novel science-based approaches to controlling transboundary and emerging diseases. The following topics are generally considered out-of-scope, but decisions are made on a case-by-case basis (for example, studies on cryptic wildlife populations, and those on potential species extinctions): Pathogen discovery: a common pathogen newly recognised in a specific country, or a new pathogen or genetic sequence for which there is little context about — or insights regarding — its emergence or spread. Prevalence estimation surveys and risk factor studies based on survey (rather than longitudinal) methodology, except when such studies are unique. Surveys of knowledge, attitudes and practices are within scope. Diagnostic test development if not accompanied by robust sensitivity and specificity estimation from field studies. Studies focused only on laboratory methods in which relevance to disease emergence and spread is not obvious or can not be inferred (“pure research” type studies). Narrative literature reviews which do not generate new knowledge. Systematic and scoping reviews, and meta-analyses are within scope.
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