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<p>Immunity by vaccination can protect human against heterologous viruses. However, protective abilities of artificial vaccines are still weaker than natural infections. Here we develop a kinetically engineered vaccine (KE-VAC) that mimics the multidimensional immunomodulation in natural infections via dynamic activation of antigen presenting cells with masked TLR7/8 agonist and sustained supplies of antigens and adjuvants to lymph nodes, leading to follicular helper T and germinal centre B cell activation in vaccinated mice. KE-VAC demonstrates superior efficacy than traditional alum and mRNA vaccines, achieving a 100% survival rate with increased neutralizing antibodies titers and polyfunctional CD8<sup>+</sup> T cells, recognizing heterologous SARS-CoV-2 variants, and inducing broad and long-term protection against multiple strains of influenza viruses. Prime/boost vaccination with KE-VAC also protect aged ferrets from severe fever with thrombocytopenia syndrome virus infection, with no virus detected in any organs at day 6 p.i. The efficacy of KE-VAC across various pathogens thus highlights its potential as an effective vaccine against emerging infectious risks.</p>

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Kinetically activating nanovaccine mimicking multidimensional immunomodulation of natural infection for broad protection against heterologous viruses in animal models

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月25日

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  • Sang Nam Lee,
  • Young-Il Kim,
  • Jaemoo Kim,
  • D. K. Haluwana,
  • Ryounho Eun,
  • Sei Hyun Park,
  • Janghun Heo,
  • Juryeon Gil,
  • Yebin Seong,
  • Min-Ho Lee,
  • Young-Woock Noh,
  • Jong-Soo Lee,
  • Young Ki Choi,
  • Yong Taik Lim

摘要

Immunity by vaccination can protect human against heterologous viruses. However, protective abilities of artificial vaccines are still weaker than natural infections. Here we develop a kinetically engineered vaccine (KE-VAC) that mimics the multidimensional immunomodulation in natural infections via dynamic activation of antigen presenting cells with masked TLR7/8 agonist and sustained supplies of antigens and adjuvants to lymph nodes, leading to follicular helper T and germinal centre B cell activation in vaccinated mice. KE-VAC demonstrates superior efficacy than traditional alum and mRNA vaccines, achieving a 100% survival rate with increased neutralizing antibodies titers and polyfunctional CD8+ T cells, recognizing heterologous SARS-CoV-2 variants, and inducing broad and long-term protection against multiple strains of influenza viruses. Prime/boost vaccination with KE-VAC also protect aged ferrets from severe fever with thrombocytopenia syndrome virus infection, with no virus detected in any organs at day 6 p.i. The efficacy of KE-VAC across various pathogens thus highlights its potential as an effective vaccine against emerging infectious risks.