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<p>This study explored the development and evaluation of mRNA vaccine candidates targeting <i>Schistosoma mansoni</i> tetraspanin-2 (<i>Sm</i>-TSP-2). We designed constructs encoding either full-length <i>Sm-</i>TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine model, the secreted and membrane-anchored versions of <i>Sm</i>-TSP-2-EC2 induced the highest antigen-specific antibody titers. These two construct designs, along with full-length <i>Sm</i>-TSP-2 mRNA, also significantly reduced adult worm and egg burden compared to controls. The membrane-anchored <i>Sm</i>-TSP-2-EC2 mRNA was the most effective, lowering worm and egg burdens by 66.7% and 66.9%, respectively. Protective responses induced by the mRNA vaccines were comparable to those elicited by the <i>Sm</i>-TSP-2-EC2 protein formulated with Alum. Histopathological analysis revealed smaller hepatic granulomas surrounding worm eggs, supporting the immunopathological benefit of vaccination. Using a systematic mRNA-based approach, we optimized the presentation of the <i>Sm</i>-TSP-2-EC2 and demonstrated that extracellular exposure of EC2 is essential for eliciting a protective response.</p>

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mRNA vaccines encoding variant forms of Sm-TSP-2 confer protective immunity against Schistosoma mansoni

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月15日

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  • Athos Silva de Oliveira,
  • Sevan Alwan,
  • Philip T. LoVerde,
  • Ramiz Shaheed,
  • Pranav Mandyam,
  • Rakesh Adhikari,
  • Peter Hotez,
  • Maria Elena Bottazzi,
  • Jeroen Pollet

摘要

This study explored the development and evaluation of mRNA vaccine candidates targeting Schistosoma mansoni tetraspanin-2 (Sm-TSP-2). We designed constructs encoding either full-length Sm-TSP-2, or its large extracellular loop (EC2) domain in secretory, membrane-anchored, or cytosolic forms. In a murine model, the secreted and membrane-anchored versions of Sm-TSP-2-EC2 induced the highest antigen-specific antibody titers. These two construct designs, along with full-length Sm-TSP-2 mRNA, also significantly reduced adult worm and egg burden compared to controls. The membrane-anchored Sm-TSP-2-EC2 mRNA was the most effective, lowering worm and egg burdens by 66.7% and 66.9%, respectively. Protective responses induced by the mRNA vaccines were comparable to those elicited by the Sm-TSP-2-EC2 protein formulated with Alum. Histopathological analysis revealed smaller hepatic granulomas surrounding worm eggs, supporting the immunopathological benefit of vaccination. Using a systematic mRNA-based approach, we optimized the presentation of the Sm-TSP-2-EC2 and demonstrated that extracellular exposure of EC2 is essential for eliciting a protective response.