2. Academic Validation
  3. Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection

Targeting vaccines to dendritic cells by mimicking the processing and presentation of antigens in xenotransplant rejection

  • Nat Biomed Eng. 2025 Feb;9(2):201-214. doi: 10.1038/s41551-025-01343-6.
Jinjin Wang # 1 2,  Yuxuan Zhang # 1 2,  Yaru Jia 1 3,  Haonan Xing 1 4,  Fengfei Xu 1 2,  Bozhang Xia 1 2,  Wenjia Lai 1,  Yuan Yuan 1,  Xianlei Li 1,  Shaobo Shan 1,  Junge Chen 1,  Weisheng Guo 5,  Jinchao Zhang 3,  Aiping Zheng 4,  Jinghong Li 6,  Ningqiang Gong 7,  Xing-Jie Liang 8 9 10 11
Affiliations

Affiliations

  • 1 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China.
  • 2 University of Chinese Academy of Sciences, Beijing, China.
  • 3 State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei University, Baoding, China.
  • 4 State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.
  • 5 School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China.
  • 6 Department of Chemistry, Center for BioAnalytical Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, New Cornerstone Science Institute, Tsinghua University, Beijing, China.
  • 7 Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China. gongn@ustc.edu.cn.
  • 8 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, China. liangxj@nanoctr.cn.
  • 9 University of Chinese Academy of Sciences, Beijing, China. liangxj@nanoctr.cn.
  • 10 State Key Laboratory of New Pharmaceutical Preparations and Excipients, Hebei University, Baoding, China. liangxj@nanoctr.cn.
  • 11 School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China. liangxj@nanoctr.cn.
  • # Contributed equally.
PMID: 39948171 DOI: 10.1038/s41551-025-01343-6
Abstract

Targeting the delivery of vaccines to dendritic cells (DCs) is challenging. Here we show that, by mimicking the fast and strong antigen processing and presentation that occurs during the rejection of xenotransplanted tissue, xenogeneic cell membrane-derived vesicles exposing tissue-specific Antibodies can be leveraged to deliver peptide antigens and mRNA-encoded antigens to DCs. In mice with murine melanoma and murine thymoma, xenogeneic vesicles encapsulating a tumour-derived antigenic peptide or coated on lipid nanoparticles encapsulating an mRNA coding for a tumour antigen elicited potent tumour-specific T-cell responses that inhibited tumour growth. Mice immunized with xenogeneic vesicle-coated lipid nanoparticles encapsulating an mRNA encoding for the spike protein of severe acute respiratory syndrome coronavirus 2 elicited titres of anti-spike receptor-binding domain immunoglobulin G and of neutralizing Antibodies that were approximately 32-fold and 6-fold, respectively, those elicited by a commercialized mRNA-lipid nanoparticle vaccine. The advantages of mimicking the biological recognition between immunoglobulin G on xenogeneic vesicles and fragment crystallizable receptors on DCs may justify the assessment of the safety risks of using animal-derived biological products in humans.

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