CD63-Mediated Antigen Delivery into Extracellular Vesicles via DNA Vaccination Results in Robust CD8+ T Cell Responses

The Journal of Immunology : Official Journal of the American Association of Immunologists
Tomohiro KanumaKen J Ishii

Abstract

DNA vaccines are attractive immunogens for priming humoral and cellular immune responses to the encoded Ag. However, their ability to induce Ag-specific CD8+ T cell responses requires improvement. Among the strategies for improving DNA vaccine immunogenicity are booster vaccinations, alternate vaccine formulations, electroporation, and genetic adjuvants, but few, such as extracellular vesicles (EVs), target natural Ag delivery systems. By focusing on CD63, a tetraspanin protein expressed on various cellular membranes, including EVs, we examined whether a DNA vaccine encoding an Ag fused to CD63 delivered into EVs would improve vaccine immunogenicity. In vitro transfection with plasmid DNA encoding an OVA Ag fused to CD63 (pCD63-OVA) produced OVA-carrying EVs. Immunizations with the purified OVA-carrying EVs primed naive mice to induce OVA-specific CD4+ and CD8+ T cells, whereas immunization with EVs purified from cells transfected with control plasmids encoding OVA protein alone or a calnexin-OVA fusion protein delivered into the endoplasmic reticulum failed to do so. Vaccinating mice with pCD63-OVA induced potent Ag-specific T cell responses, particularly those from CD8+ T cells. CD63 delivery into EVs led to better CD8+ T cel...Continue Reading

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Citations

Mar 15, 2018·Journal of Extracellular Vesicles·Yoosoo YangIn-San Kim
May 8, 2018·Blood·David Avigan, Jacalyn Rosenblatt
Sep 23, 2020·Nature Reviews. Cancer·Andreas Möller, Richard J Lobb
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Jun 24, 2021·European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery ... [et Al] = Zeitschrift Für Kinderchirurgie·Elke Zani-RuttenstockAugusto Zani
Jul 11, 2021·Molecular Immunology·Claire Drurey, Rick M Maizels
Sep 5, 2021·Journal of Hematology & Oncology·Zhijie WengLongjiang Li
Sep 10, 2021·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Santosh KumarJohn Bissler

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