HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response

作者: Paola Bonito , Barbara Ridolfi , Sandra Columba-Cabezas , Andrea Giovannelli , Chiara Chiozzini

DOI: 10.3390/V7031079

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摘要: We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production exosomes, i.e., nanovesicles spontaneously released by all types. engineered upload huge amounts upon fusion with anchoring (i.e., HIV-1 Nefmut), which is inactive incorporating in exosomes at high levels also when fused foreign proteins. compared immunogenicity uploading human papillomavirus (HPV)-E7 that lentiviral virus-like particles (VLPs) equivalent same antigen. These whose limiting membrane was decorated VSV-G, envelope inducing pH-dependent endosomal fusion, proved be as immunogenic cognate VLPs. noteworthy remained unaltered absence VSV-G. Most important, we provide evidence inoculation mouse HPV-E7 induces anti-HPV E7 CTLs, blocks growth syngeneic tumor cells inoculated after immunization, and controls development before exosome challenge. results represent proof-of-concept about both feasibility efficacy Nefmut-based platform for induction CD8+ immunity.

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