<p>The emergence of novel infectious disease has intensified demand for more advanced vaccine development and more potent adjuvants to enhance immunogenicity. Here we introduce a dynamic DNA supramolecular matrix assembled from five unmodified, short DNA single strands, serving as a safe, multifaceted adjuvant platform. This DNA matrix elicits a robust humoral response with minimal adverse effects, generating potent neutralizing antibodies and conferring robust protection against SARS-CoV-2 and <i>Streptococcus pneumoniae</i> infections. Its dynamic colloidal feature prolongs the in vivo retention of both DNA and antigen, facilitating lymphatic-targeted transportation and presentation. This process leads to a robust pro-inflammatory response in both the vaccinated site and draining lymph node, which, in turn, promotes the recruitment and activation of immune cells, leading to a rapid, effective antigen-specific antibody response. The enhanced function of DNA matrix depends on the canonical TLR9–MyD88 signalling axis in dendritic cells. In addition, only right-handed, not left-handed, chirality of the DNA strands forms <span>d</span>-DNA matrix and promotes immune activations. Thus, this DNA matrix functions as an all-in-one adjuvant platform, opening promising avenues for future vaccine design.</p>

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Enantiomer-dependent and modification-free DNA matrix as an adjuvant for subunit vaccines against SARS-CoV-2 or pneumococcal infections

  • Cuifeng Li,
  • Yuxin Li,
  • Bini Zhou,
  • Tong Li,
  • Xiaohui Wei,
  • Kun Chen,
  • Wenlong Chen,
  • Ziwei Shi,
  • Xiaobin Dai,
  • Jiachen Zhang,
  • Chen Yang,
  • Zhenglin Ji,
  • Wenbo Sun,
  • Ji Gao,
  • Jing Wu,
  • Binbin Zhao,
  • Xin Min,
  • Yujie Li,
  • Lin Lin,
  • Wei Yang,
  • Min Wang,
  • Zezhong Liu,
  • Yaping Liu,
  • Chenyou Zhu,
  • Bo Yang,
  • Jiang-Fei Xu,
  • Li-Tang Yan,
  • Yi Shi,
  • Lu Lu,
  • Linqi Zhang,
  • Qiang Ding,
  • Jing Xue,
  • Baidong Hou,
  • Hai Qi,
  • Jiangning Liu,
  • Yuhe R. Yang,
  • Dongsheng Liu,
  • Wanli Liu

摘要

The emergence of novel infectious disease has intensified demand for more advanced vaccine development and more potent adjuvants to enhance immunogenicity. Here we introduce a dynamic DNA supramolecular matrix assembled from five unmodified, short DNA single strands, serving as a safe, multifaceted adjuvant platform. This DNA matrix elicits a robust humoral response with minimal adverse effects, generating potent neutralizing antibodies and conferring robust protection against SARS-CoV-2 and Streptococcus pneumoniae infections. Its dynamic colloidal feature prolongs the in vivo retention of both DNA and antigen, facilitating lymphatic-targeted transportation and presentation. This process leads to a robust pro-inflammatory response in both the vaccinated site and draining lymph node, which, in turn, promotes the recruitment and activation of immune cells, leading to a rapid, effective antigen-specific antibody response. The enhanced function of DNA matrix depends on the canonical TLR9–MyD88 signalling axis in dendritic cells. In addition, only right-handed, not left-handed, chirality of the DNA strands forms d-DNA matrix and promotes immune activations. Thus, this DNA matrix functions as an all-in-one adjuvant platform, opening promising avenues for future vaccine design.