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<p>Antibiotics are essential for treating bacterial infections, but the growing problem of antimicrobial resistance (AMR) undermines their effectiveness. Vaccines targeting multidrug-resistant (MDR) bacteria are urgently needed. Here, we developed next-generation mRNA vaccines encoding two novel target antigens: phosphate-specific transport protein (PstS) and DUF3748 domain-containing protein (YidR). The resulting fusion proteins exhibited high expression and secretion in vitro and provided strong protective efficacy in mice against <i>Klebsiella pneumoniae (K. pneumoniae)</i> and <i>enterohemorrhagic Escherichia coli</i> (EHEC), significantly reducing bacterial loads and organ damage. Moreover, the <i>K. pneumoniae</i>-based mRNA vaccine (KV3), encoding the PstS-YidR fusion protein, elicited notable cross-protection against four <i>Enterobacteriaceae</i> species, including <i>K. pneumoniae</i>, EHEC, <i>Salmonella enterica</i> (<i>S. enterica</i>), and <i>Shigella flexneri</i> (<i>S. flexneri</i>). In conclusion, this study demonstrates the potential of mRNA vaccines employing fusion protein containing a novel target antigen to combat MDR <i>Enterobacteriaceae</i> with significant cross-protective effects.</p>

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Next-generation mRNA vaccines eliciting robust protection against multidrug-resistant Enterobacteriaceae

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月31日

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  • Rui Liu,
  • Shi Xu,
  • Shang Liu,
  • Mengwei Xu,
  • Jing Li,
  • Aili Wang,
  • Wei Li,
  • Lingzhi Zhan,
  • Keyue Ruan,
  • Caiyi Fei,
  • Zengding Wu,
  • Tiyun Han,
  • Yafei Cai

摘要

Antibiotics are essential for treating bacterial infections, but the growing problem of antimicrobial resistance (AMR) undermines their effectiveness. Vaccines targeting multidrug-resistant (MDR) bacteria are urgently needed. Here, we developed next-generation mRNA vaccines encoding two novel target antigens: phosphate-specific transport protein (PstS) and DUF3748 domain-containing protein (YidR). The resulting fusion proteins exhibited high expression and secretion in vitro and provided strong protective efficacy in mice against Klebsiella pneumoniae (K. pneumoniae) and enterohemorrhagic Escherichia coli (EHEC), significantly reducing bacterial loads and organ damage. Moreover, the K. pneumoniae-based mRNA vaccine (KV3), encoding the PstS-YidR fusion protein, elicited notable cross-protection against four Enterobacteriaceae species, including K. pneumoniae, EHEC, Salmonella enterica (S. enterica), and Shigella flexneri (S. flexneri). In conclusion, this study demonstrates the potential of mRNA vaccines employing fusion protein containing a novel target antigen to combat MDR Enterobacteriaceae with significant cross-protective effects.