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Viruses 2015, 7(3), 1079-1099; doi:10.3390/v7031079

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

1
Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
2
Department of Therapeutic Research and Medicine Evaluation, Istituto Superiore di Sanità, 00161 Rome, Italy
3
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, 00161 Rome, Italy
4
National AIDS Center, Istituto Superiore di Sanità, 00161 Rome, Italy
5
Department of Science, University Roma Tre, 00146 Rome, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Yorgo Modis
Received: 14 January 2015 / Revised: 20 February 2015 / Accepted: 28 February 2015 / Published: 9 March 2015
(This article belongs to the Special Issue Viruses and Exosomes)
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Abstract

We developed an innovative strategy to induce a cytotoxic T cell (CTL) immune response against protein antigens of choice. It relies on the production of exosomes, i.e., nanovesicles spontaneously released by all cell types. We engineered the upload of huge amounts of protein antigens upon fusion with an anchoring protein (i.e., HIV-1 Nefmut), which is an inactive protein incorporating in exosomes at high levels also when fused with foreign proteins. We compared the immunogenicity of engineered exosomes uploading human papillomavirus (HPV)-E7 with that of lentiviral virus-like particles (VLPs) incorporating equivalent amounts of the same antigen. These exosomes, whose limiting membrane was decorated with VSV-G, i.e., an envelope protein inducing pH-dependent endosomal fusion, proved to be as immunogenic as the cognate VLPs. It is noteworthy that the immunogenicity of the engineered exosomes remained unaltered in the absence of VSV-G. Most important, we provide evidence that the inoculation in mouse of exosomes uploading HPV-E7 induces production of anti-HPV E7 CTLs, blocks the growth of syngeneic tumor cells inoculated after immunization, and controls the development of tumor cells inoculated before the exosome challenge. These results represent the proof-of-concept about both feasibility and efficacy of the Nefmut-based exosome platform for the induction of CD8+ T cell immunity. View Full-Text
Keywords: exosomes; CTL immunity; HIV-1 Nef; HPV-E7; antigen cross-presentation exosomes; CTL immunity; HIV-1 Nef; HPV-E7; antigen cross-presentation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bonito, P.D.; Ridolfi, B.; Columba-Cabezas, S.; Giovannelli, A.; Chiozzini, C.; Manfredi, F.; Anticoli, S.; Arenaccio, C.; Federico, M. HPV-E7 Delivered by Engineered Exosomes Elicits a Protective CD8+ T Cell-Mediated Immune Response. Viruses 2015, 7, 1079-1099.

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