期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 17, 期 -, 页码 3325-3341出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S367494
关键词
the severe acute respiratory syndrome coronavirus-2; exosomal vaccine; T cell; epitope; human leukocyte antigen-A
资金
- National Nature Science Foundation of China [82041006]
- COVID-19 Emergency Research Fund of Zhejiang University of China [2020XGZX021]
This study successfully generated an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 and demonstrated strong CD8+ T cell response in mice. The exosomal vaccine induced significantly stronger T cell response compared to the recent cocktail vaccine.
Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response. Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-gamma spot forming units and the frequencies of IFN-gamma+/CD8+ T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.
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