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Peer-reviewedCC BYAdvanced science (Weinheim, Baden-Wurttemberg, Germany)

A Bi-Adjuvant Senolytic Nanovaccine Modulating Dendritic Cell Senescence Ameliorates Aging-Related Metabolic Dysfunction.

  • Qingxu Song1
  • Xiaoxue Du2
  • Wenbo Dong2
  • Ying Wang3
  • Xiaojing Wang3
  • Qiliang Yin4
4 affiliations
  1. 1Department of Spine Surgery, The First Hospital of Jilin University, Changchun, People's Republic of China.
  2. 2Departments of Laboratory Medicine, Lequn Branch, The First Hospital of Jilin University, Changchun, People's Republic of China.
  3. 3Medical School of Changchun Sci-Tech University, Changchun, People's Republic of China.
  4. 4Department of Geriatric Medicine, Geriatric Medicine Center, The First Hospital of Jilin University, Changchun, People's Republic of China.
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Abstract

Senolytic vaccines hold promise for eliminating senescent cells, but their efficacy is limited by poor seno-antigen immunogenicity and age-related dendritic cell (DC) dysfunction. Here, we engineered an active biomaterial-enabled bi-adjuvant senolytic nanovaccine (CK5-GC-NV) by co-assembling CpG oligodeoxynucleotide with a fusion protein of the seno-antigen Gpnmb and a cationic spider silk protein variant (CK5). Beyond antigen delivery, the CK5 scaffold acts as an intrinsic senomodulator associated with the downregulation of mitotic kinases Aurka/b and a concomitant decrease in senescence-associated PI3K/AKT phosphorylation in DCs. This intervention attenuates aged DC phenotypes, restores antigen cross-presentation, and synergizes with CpG to elicit potent cytotoxic T-lymphocyte responses against senescent targets. Across multiple aging mouse models, CK5-GC-NV immunization orchestrated targeted clearance of Gpnmb⁺ senescent adipocytes, profoundly ameliorating metabolic dysfunction and extending lifespan. This multifunctional biomaterial platform integrates seno-antigen immunogenicity enhancement with the restoration of aged DC function, providing a promising proof-of-concept for antigen-directed gerotherapeutics.

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Cite

BibTeXRIS
BibTeX
@article{song2026biadjuvant,
  title = {{A Bi-Adjuvant Senolytic Nanovaccine Modulating Dendritic Cell Senescence Ameliorates Aging-Related Metabolic Dysfunction.}},
  author = {Qingxu Song and Xiaoxue Du and Wenbo Dong and Ying Wang and Xiaojing Wang and Qiliang Yin},
  journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
  year = {2026},
  month = oct,
  doi = {10.1002/advs.78545},
  url = {https://europepmc.org/article/MED/42949633},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - A Bi-Adjuvant Senolytic Nanovaccine Modulating Dendritic Cell Senescence Ameliorates Aging-Related Metabolic Dysfunction.
AU  - Qingxu Song
AU  - Xiaoxue Du
AU  - Wenbo Dong
AU  - Ying Wang
AU  - Xiaojing Wang
AU  - Qiliang Yin
PY  - 2026
DA  - 2026/10/28
JO  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO  - 10.1002/advs.78545
UR  - https://europepmc.org/article/MED/42949633
AB  - Senolytic vaccines hold promise for eliminating senescent cells, but their efficacy is limited by poor seno-antigen immunogenicity and age-related dendritic cell (DC) dysfunction. Here, we engineered an active biomaterial-enabled bi-adjuvant senolytic nanovaccine (CK5-GC-NV) by co-assembling CpG oligodeoxynucleotide with a fusion protein of the seno-antigen Gpnmb and a cationic spider silk protein variant (CK5). Beyond antigen delivery, the CK5 scaffold acts as an intrinsic senomodulator associated with the downregulation of mitotic kinases Aurka/b and a concomitant decrease in senescence-associated PI3K/AKT phosphorylation in DCs. This intervention attenuates aged DC phenotypes, restores antigen cross-presentation, and synergizes with CpG to elicit potent cytotoxic T-lymphocyte responses against senescent targets. Across multiple aging mouse models, CK5-GC-NV immunization orchestrated targeted clearance of Gpnmb⁺ senescent adipocytes, profoundly ameliorating metabolic dysfunction and extending lifespan. This multifunctional biomaterial platform integrates seno-antigen immunogenicity enhancement with the restoration of aged DC function, providing a promising proof-of-concept for antigen-directed gerotherapeutics.
SN  - 2198-3844
ER  -