Ma Jun, Xiao Xun, Zhou Yanrong, Huang Wen, Sun Jie, Chang Xinjian, Xiao Shaobo, Fang Liurong
National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
The Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
J Nanobiotechnology. 2025 Jun 12;23(1):438. doi: 10.1186/s12951-025-03514-8.
Coinfection with multiple viruses is a common occurrence in the pig industry. Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) are two significant pathogens, with a notable prevalence of their coinfection observed in clinical settings. However, reports on corresponding combination vaccines against PRRSV and PCV2 are scarce. The capsid (Cap) protein encoded by PCV2 is highly immunogenic, and recombinant Cap expressed in vitro can self-assemble into virus-like particles (VLPs), providing a promising strategy for developing bivalent vaccines against both PRRSV and PCV2.
Three novel nanoparticle vaccines (Cap-DS, Cap-DP, and Cap-DE) were engineered by inserting multiple neutralizing epitopes from PRRSV (GP5B epitope, GP3I epitope, and GP5IV epitope) into the PCV2 Cap protein. These recombinant proteins, produced using a baculovirus expression system, successfully formed VLPs in vitro.
Immunization of BALB/c mice with these nanoparticle vaccines significantly enhanced T-lymphocyte immune responses and elicited high-titer antibodies against both PCV2 and PRRSV. Notably, Cap-DS induced more potent serum neutralizing antibodies against PRRSV compared to Cap-DP and Cap-DE. Piglets immunized with Cap-DS, upon challenge with PRRSV, demonstrated significant protection compared to the PBS-immunized control group.
These findings indicate that Cap-DS is a promising candidate for the development of a bivalent nanoparticle vaccine against PRRSV and PCV2 infections, addressing a significant gap in current swine vaccination strategies.
多种病毒的混合感染在养猪业中很常见。猪繁殖与呼吸综合征病毒(PRRSV)和猪圆环病毒2型(PCV2)是两种重要的病原体,在临床环境中观察到它们混合感染的发生率很高。然而,针对PRRSV和PCV2的相应联合疫苗的报道却很少。PCV2编码的衣壳(Cap)蛋白具有高度免疫原性,体外表达的重组Cap可自组装成病毒样颗粒(VLP),为开发针对PRRSV和PCV2的二价疫苗提供了一种有前景的策略。
通过将来自PRRSV的多个中和表位(GP5B表位、GP3I表位和GP5IV表位)插入PCV2 Cap蛋白中,构建了三种新型纳米颗粒疫苗(Cap-DS、Cap-DP和Cap-DE)。这些重组蛋白利用杆状病毒表达系统生产,在体外成功形成了VLP。
用这些纳米颗粒疫苗免疫BALB/c小鼠可显著增强T淋巴细胞免疫反应,并引发针对PCV2和PRRSV的高滴度抗体。值得注意的是,与Cap-DP和Cap-DE相比,Cap-DS诱导产生的针对PRRSV的血清中和抗体更强。用Cap-DS免疫的仔猪在受到PRRSV攻击后,与接种PBS的对照组相比,表现出显著的保护作用。
这些发现表明,Cap-DS是开发针对PRRSV和PCV2感染的二价纳米颗粒疫苗的有前景的候选物,填补了当前猪疫苗接种策略中的一个重大空白。