Wu Weixin, Fang Xinyu, Jiang Yiyao, Hu Jiameng, Zhou Qiongqiong, Gao Peng, Zhang Yongning, Ge Xinna, Han Jun, Guo Xin, Zhou Lei, Yang Hanchun
National Key Laboratory of Veterinary Public Health Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory of Animal Epidemiology of Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Front Immunol. 2025 May 8;16:1585197. doi: 10.3389/fimmu.2025.1585197. eCollection 2025.
Porcine reproductive and respiratory syndrome (PRRS), caused by the PRRS virus (PRRSV), is an economically significant swine disease with extensive strain variation and limited heterologous protection. Modified live virus (MLV) vaccines developed by serially passaging the virus in monkey kidney cell lines have been widely used for more than 20 years. Lineage 1 virus, such as NADC30-like in China and L1C 1-4-4 strains in the United States, have gradually become the predominant strain or the dominant recombination isolate donor strain in recent years. MLVs licensed for use in the market supply low efficacy of heterologous protection ability against the NADC30-like strain, and a vaccine with improved safety and efficacy is therefore required. The method of virulence attenuation used for classical strains may not be applicable to the development of a vaccine against NADC30-like strains due to their low fidelity of replication.
Chimeric RvBJ-4-(ORF2-4)SX, RvBJ-4-(ORF5-6)SX, and RvBJ-4-(ORF2-6)SX were constructed by substituting minor structural proteins (GP2, GP3, and GP4), major structural proteins (GP5 and M) or both in NADC30-like CHsx1401 to classical strain backbone BJ-4. RvBJ-4-(ORF2-6)SX. Animal trials were conducted to assess the pathogenicity and protection of chimeric viruses.
Chimeric virus RvBJ-4-(ORF2-6)SX demonstrates a favorable balance between safety and efficacy, with limited pathogenicity and providing faster viremia clearance as well as reduced lung lesions in vaccinated/challenged pigs. A novel strategy for providing safe and effective immunological protection against NADC30-like strains has been introduced, with the potential for implementation in the field.
猪繁殖与呼吸综合征（PRRS）由猪繁殖与呼吸综合征病毒（PRRSV）引起，是一种具有重大经济影响的猪病，毒株变异广泛且异源保护有限。通过在猴肾细胞系中连续传代培养病毒而研发的改良活病毒（MLV）疫苗已广泛使用20多年。近年来，1型毒株，如中国的NADC30样毒株和美国的L1C 1-4-4毒株，已逐渐成为主要毒株或主要重组分离供体毒株。市场上许可使用的MLV对NADC30样毒株的异源保护能力效力较低，因此需要一种安全性和效力更高的疫苗。由于NADC30样毒株复制的低保真性，用于经典毒株的毒力减弱方法可能不适用于研发针对NADC30样毒株的疫苗。
通过将NADC30样CHsx1401中的次要结构蛋白（GP2、GP3和GP4）、主要结构蛋白（GP5和M）或两者替换为经典毒株骨架BJ-4，构建嵌合病毒RvBJ-4-(ORF2-4)SX、RvBJ-4-(ORF5-6)SX和RvBJ-4-(ORF2-6)SX。对RvBJ-4-(ORF2-6)SX进行动物试验，以评估嵌合病毒的致病性和保护作用。
嵌合病毒RvBJ-4-(ORF2-6)SX在安全性和效力之间展现出良好平衡，致病性有限，能使接种/攻毒猪更快清除病毒血症，并减少肺部病变。已引入一种针对NADC30样毒株提供安全有效免疫保护的新策略，具有在实际应用中的潜力。
