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Nature Biomedical Engineering · 2025 · IF 26.6

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

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

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.

研究领域: 免疫学 · 微生物学 · 生物材料 · 疫苗学
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