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<p>Although injectable respiratory syncytial virus (RSV) pre-F vaccines are clinically established, effective intranasal alternatives remain elusive. Geometric and surface antigen display properties are critical for respiratory B cell activation, yet lack strategies for systematic optimization. Here we report a library of DNA nanocarriers with controlled dimensions and sizes, aiming to systemically evaluate the influence of geometric properties on intranasal retention. Taking advantage of the precise control on DNA nanocarriers and antigen functionalization, we organized the surface antigen patterns of pre-F monomers on DNA nanocarriers to maximize B cell activation. The optimized DNA nanocarrier-based vaccine elicited humoral immunity in mice comparable to that induced by the clinically approved trimeric mRNA vaccine against RSV, but with greater durability. While intramuscular mRNA vaccines failed to induce effective respiratory mucosal immunity, the intranasal DNA nanocarrier-based vaccine achieved robust local and systemic immune activation, conferring potent protection against RSV infection. This rational design of intranasal RSV vaccines may be a general strategy for testing and advancing potent intranasal vaccines for a range of infectious respiratory diseases.</p>

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Intranasal DNA nanocarrier vaccines with surface-patterned antigens enhance efficacy against respiratory syncytial virus

  • 期刊论文

  • 发表日期：

    2026年7月1日

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  • Xiaoyu Gao,
  • Liting Chen,
  • Qingqing Feng,
  • Wei Lv,
  • Peijun Xu,
  • Zetao Yu,
  • Xinwei Wang,
  • Qinyi Zhang,
  • Tianyu Shao,
  • Yichao Lu,
  • Wenna Li,
  • Jiabeini Zhang,
  • Dingfei Qian,
  • Xinze Du,
  • Jiajia Zou,
  • Linjie Chen,
  • Guangjun Nie,
  • Keman Cheng,
  • Xiao Zhao

摘要

Although injectable respiratory syncytial virus (RSV) pre-F vaccines are clinically established, effective intranasal alternatives remain elusive. Geometric and surface antigen display properties are critical for respiratory B cell activation, yet lack strategies for systematic optimization. Here we report a library of DNA nanocarriers with controlled dimensions and sizes, aiming to systemically evaluate the influence of geometric properties on intranasal retention. Taking advantage of the precise control on DNA nanocarriers and antigen functionalization, we organized the surface antigen patterns of pre-F monomers on DNA nanocarriers to maximize B cell activation. The optimized DNA nanocarrier-based vaccine elicited humoral immunity in mice comparable to that induced by the clinically approved trimeric mRNA vaccine against RSV, but with greater durability. While intramuscular mRNA vaccines failed to induce effective respiratory mucosal immunity, the intranasal DNA nanocarrier-based vaccine achieved robust local and systemic immune activation, conferring potent protection against RSV infection. This rational design of intranasal RSV vaccines may be a general strategy for testing and advancing potent intranasal vaccines for a range of infectious respiratory diseases.