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<p><i>Lactiplantibacillus plantarum</i>, recognized for its potent probiotic functionality and advanced drug delivery capability, has emerged as a versatile platform for the heterologous expression of bioactive therapeutic proteins. In this study, we genetically engineered <i>L. plantarum</i> to express interferon-induced transmembrane protein 3 (IFITM3), an immunomodulatory protein that exhibits extensive antiviral efficacy by predominantly obstructing viral entry. To enhance gastrointestinal resilience and systemic bioavailability, the recombinant strain was encapsulated with hyaluronic acid (HA-r-LAB) through a precise nanoencapsulation methodology, generating stable nanoparticle-like constructs. In a piglet model challenged with transmissible gastroenteritis virus (TGEV), a prototypical coronavirus, oral administration of HA-r-LAB expressing IFITM3 substantially decreased viral titres and alleviated clinical manifestations. Furthermore, biochemical analyses confirmed a direct molecular interaction between IFITM3 and the TGEV nucleocapsid (N) protein, suggesting an unprecedented antiviral mechanism. These findings underscore the potential of HA-r-LAB as a probiotic-based nanodelivery vector for antiviral proteins and lay the groundwork for the development of combinatorial therapeutic strategies targeting coronaviruses.</p>

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IFITM3-expressing Lactobacillus plantarum (HA-r-LAB) as a probiotic vector for targeted immunotherapy against TGEV

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Binghan Bai,
  • Maokun Zhu,
  • Ling Zhang,
  • Lixin Wen,
  • Xiaomin Yuan

摘要

Lactiplantibacillus plantarum, recognized for its potent probiotic functionality and advanced drug delivery capability, has emerged as a versatile platform for the heterologous expression of bioactive therapeutic proteins. In this study, we genetically engineered L. plantarum to express interferon-induced transmembrane protein 3 (IFITM3), an immunomodulatory protein that exhibits extensive antiviral efficacy by predominantly obstructing viral entry. To enhance gastrointestinal resilience and systemic bioavailability, the recombinant strain was encapsulated with hyaluronic acid (HA-r-LAB) through a precise nanoencapsulation methodology, generating stable nanoparticle-like constructs. In a piglet model challenged with transmissible gastroenteritis virus (TGEV), a prototypical coronavirus, oral administration of HA-r-LAB expressing IFITM3 substantially decreased viral titres and alleviated clinical manifestations. Furthermore, biochemical analyses confirmed a direct molecular interaction between IFITM3 and the TGEV nucleocapsid (N) protein, suggesting an unprecedented antiviral mechanism. These findings underscore the potential of HA-r-LAB as a probiotic-based nanodelivery vector for antiviral proteins and lay the groundwork for the development of combinatorial therapeutic strategies targeting coronaviruses.