基于展示猪圆环病毒2型和3型衣壳蛋白的mi3的二价纳米颗粒的构建和免疫原性评估
Construction and immunogenicity evaluation of a bivalent nanoparticle based on mi3 displaying porcine circovirus type 2 and type 3 capsid proteins.
Construction and immunogenicity evaluation of a bivalent nanoparticle based on mi3 displaying porcine circovirus type 2 and type 3 capsid proteins.
猪圆环病毒2型(PCV2)和3型(PCV3)对全球猪群健康构成严重威胁。PCV2野毒株随着多种基因型的共循环而持续变异,导致其可能逃避现有疫苗的免疫保护。PCV3作为一种新发病原体,目前尚无市售疫苗。临床上,PCV2与PCV3混合感染十分普遍,因此迫切需要一种二价疫苗。本研究旨在基于mi3纳米笼构建广谱、高效的双价纳米颗粒抗原(PCV2-PCV3 Nano),并评估其免疫效力。首先,通过分析当前流行毒株,对PCV2和PCV3衣壳(Cap)蛋白的氨基酸序列进行优化。将SpyCatcher(SC)或SpyTag(ST)结构域分别与mi3、PCV2 Cap或PCV3 Cap进行基因融合。融合序列经密码子优化后在大肠杆菌中异源表达。纯化后,通过SC-ST生物偶联将PCV2 Cap和PCV3 Cap共价锚定于mi3纳米笼上,成功构建了PCV2-PCV3 Nano。BALB/c小鼠免疫试验表明,与常规抗原和商品化PCV2疫苗相比,PCV2-PCV3 Nano可显著诱导更高的抗体水平,并对PCV2b、PCV2d和PCV3感染提供免疫保护。本研究为PCV2-PCV3 Nano的产业化应用奠定了重要基础,并为基于mi3的多价疫苗开发提供了技术支持。
Porcine circovirus type 2 (PCV2) and type 3 (PCV3) pose severe threats to swine health worldwide. PCV2 field strains continuously mutate with the co-circulation of multiple genotypes, resulting in potential immune escape from existing vaccines. PCV3, an emerging pathogen, currently has no commercially available vaccines. Clinically, PCV2-PCV3 co-infection is prevalent, thus highlighting an urgent need for a bivalent vaccine. This study aimed to construct a broad-spectrum, high-efficiency bivalent nanoparticle antigen (PCV2-PCV3 Nano) based on mi3 nanocages and to evaluate its immunological efficacy. First, amino acid sequences of PCV2 and PCV3 capsid (Cap) proteins were optimized through analysis of currently prevalent strains. SpyCatcher (SC) or SpyTag (ST) domains were genetically fused to mi3, PCV2 Cap, or PCV3 Cap, respectively. The fusion sequences were codon-optimized and heterologously expressed in . After purification, PCV2 Cap and PCV3 Cap were covalently anchored onto mi3 nanocages via SC-ST bioconjugation, successfully constructing PCV2-PCV3 Nano. Immunization of BALB/c mice demonstrated that PCV2-PCV3 Nano significantly induced higher antibody levels and conferred immune protection against PCV2b, PCV2d, and PCV3 infections compared with conventional antigens and commercial PCV2 vaccines. This study establishes a critical foundation for the industrial application of PCV2-PCV3 Nano, and it provides technical support for the development of mi3-based multivalent vaccines.
Baishi Lei, Jiale Du, Yiran Li, Yuchuan Yang, Peng Chen, Longhai Ji, et al. Construction and immunogenicity evaluation of a bivalent nanoparticle based on mi3 displaying porcine circovirus type 2 and type 3 capsid proteins.. Frontiers in veterinary science. 2026; doi:10.3389/fvets.2026.1862938.
Baishi Lei, Jiale Du, Yiran Li, Yuchuan Yang, Peng Chen, Longhai Ji, et al (2026). Construction and immunogenicity evaluation of a bivalent nanoparticle based on mi3 displaying porcine circovirus type 2 and type 3 capsid proteins.. Frontiers in veterinary science. https://doi.org/10.3389/fvets.2026.1862938
Baishi Lei, Jiale Du, Yiran Li, Yuchuan Yang, Peng Chen, Longhai Ji, et al. Construction and immunogenicity evaluation of a bivalent nanoparticle based on mi3 displaying porcine circovirus type 2 and type 3 capsid proteins.[J]. Frontiers in veterinary science, 2026 doi:10.3389/fvets.2026.1862938.
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