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 language | English |
|---|---|
| Pages (from-to) | 773-782 |
| Number of pages | 10 |
| Journal | Molecular Biotechnology |
| Volume | 60 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2018 |
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Keywords
- Exosomes
- HBV
- Tumors
- Aids patients
ASJC Scopus subject areas
- Biotechnology
- Bioengineering
- Biochemistry
- Applied Microbiology and Biotechnology
- Molecular Biology
Cite this
DNA Vectors Generating Engineered Exosomes Potential CTL Vaccine Candidates Against AIDS, Hepatitis B, and Tumors. / Ferrantelli, Flavia; Manfredi, Francesco; Chiozzini, Chiara; Anticoli, Simona; Olivetta, Eleonora; Arenaccio, Claudia; Federico, Maurizio.
In: Molecular Biotechnology, Vol. 60, No. 11, 01.11.2018, p. 773-782.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - DNA Vectors Generating Engineered Exosomes Potential CTL Vaccine Candidates Against AIDS, Hepatitis B, and Tumors
AU - Ferrantelli, Flavia
AU - Manfredi, Francesco
AU - Chiozzini, Chiara
AU - Anticoli, Simona
AU - Olivetta, Eleonora
AU - Arenaccio, Claudia
AU - Federico, Maurizio
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Exosomes
KW - HBV
KW - Tumors
KW - Aids patients
UR - http://www.scopus.com/inward/record.url?scp=85052783939&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052783939&partnerID=8YFLogxK
U2 - 10.1007/s12033-018-0114-3
DO - 10.1007/s12033-018-0114-3
M3 - Article
C2 - 30167966
AN - SCOPUS:85052783939
VL - 60
SP - 773
EP - 782
JO - Molecular Biotechnology
JF - Molecular Biotechnology
SN - 1073-6085
IS - 11
ER -