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<p>Canine distemper virus (CDV) is a highly contagious morbillivirus that causes severe disease in carnivores, with raccoon dogs (Nyctereutes procyonoides) serving as major reservoirs for transmission. To address the limitations of current vaccines—such as virulence reversion, multiple doses, and poor efficacy in raccoon dogs—we developed a novel mRNA–lipid nanoparticle (LNP) vaccine encoding a secreted, tetrameric CDV hemagglutinin (H) protein fused to a signal peptide and Tetrabrachion domain to enhance stability and immunogenicity. The vaccine showed high purity, uniform particle size (~108 nm), and efficient in vivo expression of glycosylated H protein. In BALB/c mice, it induced strong H-specific IgG and increased splenic CD4⁺ T cells, suggesting a Th-skewed immune response. In raccoon dogs, high neutralizing antibody titers were maintained post-immunization, and all vaccinated animals survived lethal CDV challenge, whereas controls showed 100% mortality. Compared with a live-attenuated CDV vaccine, the mRNA–LNP vaccine markedly reduced clinical signs, preserved intestinal integrity, and nearly eliminated viral RNA in mucosal and systemic tissues. This study provides the first evidence that an mRNA-LNP vaccine encoding CDV hemagglutinin can confer complete protection against CDV challenge in raccoon dogs, highlighting its potential for veterinary and wildlife disease prevention.</p>

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mRNA-LNP vaccine encoding CDV hemagglutinin confers effective protection in raccoon dogs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月14日

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  • Chengqi Zhang,
  • Tiyun Han,
  • Dingrui Guo,
  • Shuangshuang Li,
  • Wenyu Cao,
  • Xiaolan Guo,
  • Zichaung Zhang,
  • Jiajia Liu,
  • Yajie Sun,
  • Liwen Xu,
  • Ping Ma,
  • Mengwei Xu,
  • Jing Li,
  • Shi Xu,
  • Bo Hu,
  • Xue Bai

摘要

Canine distemper virus (CDV) is a highly contagious morbillivirus that causes severe disease in carnivores, with raccoon dogs (Nyctereutes procyonoides) serving as major reservoirs for transmission. To address the limitations of current vaccines—such as virulence reversion, multiple doses, and poor efficacy in raccoon dogs—we developed a novel mRNA–lipid nanoparticle (LNP) vaccine encoding a secreted, tetrameric CDV hemagglutinin (H) protein fused to a signal peptide and Tetrabrachion domain to enhance stability and immunogenicity. The vaccine showed high purity, uniform particle size (~108 nm), and efficient in vivo expression of glycosylated H protein. In BALB/c mice, it induced strong H-specific IgG and increased splenic CD4⁺ T cells, suggesting a Th-skewed immune response. In raccoon dogs, high neutralizing antibody titers were maintained post-immunization, and all vaccinated animals survived lethal CDV challenge, whereas controls showed 100% mortality. Compared with a live-attenuated CDV vaccine, the mRNA–LNP vaccine markedly reduced clinical signs, preserved intestinal integrity, and nearly eliminated viral RNA in mucosal and systemic tissues. This study provides the first evidence that an mRNA-LNP vaccine encoding CDV hemagglutinin can confer complete protection against CDV challenge in raccoon dogs, highlighting its potential for veterinary and wildlife disease prevention.