DNA Vectors Generating Engineered Exosomes Potential CTL Vaccine Candidates Against AIDS, Hepatitis B, and Tumors

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Abstract

Eukaryotic cells constitutively produce nanovesicles of 50–150 nm of diameter, referred to as exosomes, upon release of the contents of multivesicular bodies (MVBs). We recently characterized a novel, exosome-based way to induce cytotoxic T lymphocyte (CTL) immunization against full-length antigens. It is based on DNA vectors expressing products of fusion between the exosome-anchoring protein Nef mutant (Nefmut) with the antigen of interest. The strong efficiency of Nefmut to accumulate in MVBs results in the production of exosomes incorporating huge amounts of the desired antigen. When translated in animals, the injection of Nefmut-based DNA vectors generates engineered exosomes whose internalization in antigen-presenting cells induces cross-priming and antigen-specific CTL immunity. Here, we describe the molecular strategies we followed to produce DNA vectors aimed at generating immunogenic exosomes potentially useful to elicit a CTL immune response against antigens expressed by the etiologic agents of major chronic viral infections, i.e., HIV-1, HBV, and the novel tumor-associated antigen HOXB7. Unique methods intended to counteract intrinsic RNA instability and nuclear localization of the antigens have been developed. The success we met with the production of these engineered exosomes opens the way towards pre-clinic experimentations devoted to the optimization of new vaccine candidates against major infectious and tumor pathologies.

Original languageEnglish
Pages (from-to)773-782
Number of pages10
JournalMolecular Biotechnology
Volume60
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Exosomes
Vaccines
T-cells
Cytotoxic T-Lymphocytes
Antigens
Hepatitis B
Tumors
Acquired Immunodeficiency Syndrome
DNA
Neoplasms
Multivesicular Bodies
nef Gene Products
Cross-Priming
Immunization
Nuclear Antigens
Histocompatibility Antigens Class II
RNA Stability
Eukaryotic Cells
Neoplasm Antigens
Pathology

Keywords

  • Exosomes
  • HBV
  • Tumors
  • Aids patients

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology
  • Molecular Biology

Cite this

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title = "DNA Vectors Generating Engineered Exosomes Potential CTL Vaccine Candidates Against AIDS, Hepatitis B, and Tumors",
abstract = "Eukaryotic cells constitutively produce nanovesicles of 50–150 nm of diameter, referred to as exosomes, upon release of the contents of multivesicular bodies (MVBs). We recently characterized a novel, exosome-based way to induce cytotoxic T lymphocyte (CTL) immunization against full-length antigens. It is based on DNA vectors expressing products of fusion between the exosome-anchoring protein Nef mutant (Nefmut) with the antigen of interest. The strong efficiency of Nefmut to accumulate in MVBs results in the production of exosomes incorporating huge amounts of the desired antigen. When translated in animals, the injection of Nefmut-based DNA vectors generates engineered exosomes whose internalization in antigen-presenting cells induces cross-priming and antigen-specific CTL immunity. Here, we describe the molecular strategies we followed to produce DNA vectors aimed at generating immunogenic exosomes potentially useful to elicit a CTL immune response against antigens expressed by the etiologic agents of major chronic viral infections, i.e., HIV-1, HBV, and the novel tumor-associated antigen HOXB7. Unique methods intended to counteract intrinsic RNA instability and nuclear localization of the antigens have been developed. The success we met with the production of these engineered exosomes opens the way towards pre-clinic experimentations devoted to the optimization of new vaccine candidates against major infectious and tumor pathologies.",
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author = "Flavia Ferrantelli and Francesco Manfredi and Chiara Chiozzini and Simona Anticoli and Eleonora Olivetta and Claudia Arenaccio and Maurizio Federico",
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AU - Ferrantelli, Flavia

AU - Manfredi, Francesco

AU - Chiozzini, Chiara

AU - Anticoli, Simona

AU - Olivetta, Eleonora

AU - Arenaccio, Claudia

AU - Federico, Maurizio

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