Journal
JOURNAL OF EXTRACELLULAR VESICLES
Volume 11, Issue 3, Pages -Publisher
WILEY
DOI: 10.1002/jev2.12199
Keywords
extracellular vesicle; immunogenicity; transmembrane domain; viral glycoprotein
Categories
Funding
- Engineering and Physical Sciences Research Council [EP/R013764/1]
- H2020 Marie Sklodowska-Curie Actions [794059]
- UK Regenerative Medicine Platform [MR/R015651/1]
- Wellcome Trust [209121_Z_17_Z]
- Cancer Research UK [A26234]
- Swiss National Science Foundation [P2EZP2_199862]
- Wellcome Trust [209121/Z/17/Z] Funding Source: Wellcome Trust
- Swiss National Science Foundation (SNF) [P2EZP2_199862] Funding Source: Swiss National Science Foundation (SNF)
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This study found that viral transmembrane domains can efficiently load antigens onto the surface of extracellular vesicles (EVs), and that EV-bound antigens enhance both humoral and cell-mediated antigen-specific responses.
A vaccine antigen, when launched as DNA or RNA, can be presented in various forms, including intracellular, secreted, membrane-bound, or on extracellular vesicles (EVs). Whether an antigen in one or more of these forms is superior in immune induction remains unclear. In this study, we used GFP as a model antigen and first compared the EV-loading efficiency of transmembrane domains (TMs) from various viral glycoproteins, and then investigated whether EV-bound GFP (EV-GFP) would enhance immune induction. Our data showed that GFP fused to viral TMs was successfully loaded onto the surface of EVs. In addition, GFP-bound EVs were predominantly associated with the exosome marker CD81. Immunogenicity study with EV-GFP-producing plasmids in mice demonstrated that antigen-specific IgG and IgA were significantly increased in EV-GFP groups, compared to soluble and intracellular GFP groups. Similarly, GFP-specific T cell response-related cytokines produced by antigen-stimulated splenocytes were also enhanced in mice immunized with EV-GFP constructs. Immunogenicity study with purified soluble GFP and GFP EVs further confirmed the immune enhancement property of EV-GFP in mice. In vitro uptake assays indicated that EV-GFP was more efficiently taken up than soluble GFP by mouse splenocytes and such uptake was B cell preferential. Taken together, our data indicate that viral TMs can efficiently load antigens onto the EV surface, and that EV-bound antigen enhances both humoral and cell-mediated antigen-specific responses.
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