Attenuation of a contemporary Chinese PRRSV-1 strain via serial cell passage and evaluation of its protective efficacy as a modified live virus vaccine candidate

IF 2.6 3区医学 Q3 VIROLOGY

Virology Pub Date : 2026-02-01 Epub Date: 2025-11-29 DOI:10.1016/j.virol.2025.110746

Jianming Long , Keyi Liu , Yiting Chen , Xindong Wang , Zhiying Su , Guoyang Li , Kang Zhang , Tongwei Ren , Yifeng Qin , Kang Ouyang , Ying Chen , Weijian Huang , Yeshi Yin , Yingyi Wei , Zuzhang Wei

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引用次数: 0

Abstract

Porcine Reproductive and Respiratory Syndrome Virus type 1 (PRRSV-1) imposes substantial economic burdens on global swine production. In China, where only subtype 1 strains circulate across 23 provinces, evolving subpopulations challenge existing control measures. The absence of licensed PRRSV-1 vaccines in China underscores the urgency of developing tailored vaccine candidates against circulating strains. This study attenuated a contemporary Chinese PRRSV-1 isolate (GXFS20220129) through 100 serial passages (P100) on MARC-145 cells and evaluated its efficacy as a modified live virus (MLV) candidate. In vitro characterization revealed enhanced growth kinetics and increased plaque morphology in P100. Whole-genome sequencing identified 37 nucleotide mutations and 19 amino acid substitutions in P100, concentrated in the nsp1-3 and GP2 regions, potentially associated with attenuation. Immunogenicity and protection were assessed in piglets. The P100-immunized group exhibited no clinical signs post-challenge, maintained weight gain equivalent to blank controls, and demonstrated robust seroconversion by 14 dpi. The area under the curve (AUC) analyses (28–42 dpi) showed significantly lower nasal-shedding and higher antibody responses in vaccinated pigs, whereas cumulative viremia and rectal-shedding AUCs were not significantly different between challenged groups. Vaccination attenuated viremia, accelerated viral clearance, significantly reduced viral loads in systemic tissues (heart, liver, lung, kidney) and intestinal segments (duodenum, ileum, rectum), and altered shedding kinetics. Gross and histopathological lesions in lungs and intestines were substantially mitigated in immunized animals. Collectively, serial passage generated an attenuated PRRSV-1 strain conferring comprehensive protection against homologous challenge, supporting its potential as an MLV candidate for PRRSV-1 control in China.

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当代中国一株PRRSV-1的细胞连续传代衰减及其作为修饰活病毒候选疫苗的保护效果评价

猪繁殖与呼吸综合征病毒1型（PRRSV-1）给全球生猪生产带来了巨大的经济负担。在中国，只有1型毒株在23个省份传播，不断演变的亚群对现有的控制措施构成挑战。中国缺乏获得许可的PRRSV-1疫苗，这凸显了开发针对流行毒株的定制候选疫苗的紧迫性。本研究通过100次连续传代（P100）对中国当代PRRSV-1分离物GXFS20220129在MARC-145细胞上进行减毒，并评估其作为修饰活病毒（MLV）候选物的效力。体外表征显示P100的生长动力学增强，斑块形态增加。全基因组测序鉴定出P100中37个核苷酸突变和19个氨基酸替换，集中在nsp1-3和GP2区域，可能与衰减有关。对仔猪进行免疫原性和保护性评价。p100免疫组在攻击后没有表现出任何临床症状，保持与空白对照组相当的体重增加，并表现出14 dpi的强劲血清转化。曲线下面积（AUC）分析（28-42 dpi）显示，接种猪的鼻脱落显著降低，抗体反应显著提高，而累积病毒血症和直肠脱落AUC在攻毒组之间无显著差异。疫苗可减轻病毒血症，加速病毒清除，显著降低全身组织（心、肝、肺、肾）和肠段（十二指肠、回肠、直肠）的病毒载量，并改变脱落动力学。免疫动物肺和肠的大体和组织病理学病变明显减轻。总的来说，序列传代产生了一个减毒的PRRSV-1菌株，对同源攻击具有全面的保护作用，支持其作为中国PRRSV-1控制的MLV候选株的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Virology 医学-病毒学

CiteScore

6.00

自引率

0.00%

发文量

157

审稿时长

50 days

期刊介绍： Launched in 1955, Virology is a broad and inclusive journal that welcomes submissions on all aspects of virology including plant, animal, microbial and human viruses. The journal publishes basic research as well as pre-clinical and clinical studies of vaccines, anti-viral drugs and their development, anti-viral therapies, and computational studies of virus infections. Any submission that is of broad interest to the community of virologists/vaccinologists and reporting scientifically accurate and valuable research will be considered for publication, including negative findings and multidisciplinary work.Virology is open to reviews, research manuscripts, short communication, registered reports as well as follow-up manuscripts.