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Nanoparticle Vaccine Triggers Interferon-Gamma Production and Confers Protective Immunity against Porcine Reproductive and Respiratory Syndrome Virus
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    Nanoparticle Vaccine Triggers Interferon-Gamma Production and Confers Protective Immunity against Porcine Reproductive and Respiratory Syndrome Virus
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    • Yangyang Sun
      Yangyang Sun
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
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    • Yanni Gao
      Yanni Gao
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      More by Yanni Gao
    • Tongjian Su
      Tongjian Su
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      More by Tongjian Su
    • Lujie Zhang
      Lujie Zhang
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      More by Lujie Zhang
    • Haoran Zhou
      Haoran Zhou
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      More by Haoran Zhou
    • Jie Zhang
      Jie Zhang
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      More by Jie Zhang
    • Haifeng Sun
      Haifeng Sun
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
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    • Juan Bai
      Juan Bai
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China
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    • Ping Jiang*
      Ping Jiang
      Key Laboratory of Animal Disease Diagnostics and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
      Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China
      *Email: [email protected]
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    ACS Nano

    Cite this: ACS Nano 2025, 19, 1, 852–870
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    https://doi.org/10.1021/acsnano.4c12212
    Published January 6, 2025
    Copyright © 2025 American Chemical Society

    Abstract

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    The swine industry annually suffers significant economic losses caused by porcine reproductive and respiratory syndrome virus (PRRSV). Because the available commercial vaccines have limited protective efficacy against epidemic PRRSV, there is an urgent need for innovative solutions. Nanoparticle vaccines induce robust immune responses and have become a promising direction in vaccine development. In this study, we designed and produced a self-assembling nanoparticle vaccine derived from thermophilic archaeal ferritin to combat epidemic PRRSV. First, multiple T cell epitopes targeting viral structural proteins were identified by IFN-γ screening after PRRSV infection. Three different self-assembled nanoparticles with epitopes targeting viral GP3, GP4, and GP5 proteins were constructed and mixed to generate a FeCocktail vaccine. Experiments showed that the FeCocktail vaccine effectively activated CD4+ and CD8+ T cells and effector memory T cells in mice. Piglets immunized with the FeCocktail vaccine generated specific antibodies and exhibited increased levels of PRRSV-specific IFN-γ produced by functional CD4+ and CD8+ cells. The FeCocktail also provided protective efficacy against PRRSV challenge, including mitigation of clinical symptoms, reduction of viral loads in serum and lungs, and the alleviation of lung tissue damage. In conclusion, this study offers a promising candidate vaccine for combating epidemic PRRSV, and affirms the utility of nanoparticle protein as a platform for next-generation PRRSV vaccine development.

    Copyright © 2025 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.4c12212.

    • Identification of potential T cell epitopes in synthesized peptides by ELISpot assay; Multiple sequence alignment of T cell epitopes identified in type 2 PRRSV strains; properties of PRRSV structural proteins; further characterization of GP4m-SpyCatcher; the optimal conjugation ratios of the three SpyCatcher protein with SpyTag-Ferritin; the conjugation efficiency of the three SpyCatcher protein with SpyTag-Ferritin; gating strategy to distinguish T cell types obtained from mouse spleens; gating strategy to distinguish various T cells obtained from piglet peripheral blood mononuclear cells; cytotoxicity of ferritin-based nanoparticles on macrophages; hemolysis assay results; serum biochemistry assay results; synthesis of peptides used to stimulate PBMCs; overview of T cell epitopes in PRRSV structural proteins; overview of B cell epitopes in PRRSV structural proteins (PDF)

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    ACS Nano

    Cite this: ACS Nano 2025, 19, 1, 852–870
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acsnano.4c12212
    Published January 6, 2025
    Copyright © 2025 American Chemical Society

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