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Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.

Publication ,  Journal Article
Bona, R; Michelini, Z; Mazzei, C; Gallinaro, A; Canitano, A; Borghi, M; Vescio, MF; Di Virgilio, A; Pirillo, MF; Klotman, ME; Negri, D; Cara, A
Published in: Mol Ther Methods Clin Dev
December 10, 2021

Integrase-defective lentiviral vectors (IDLVs) represent an attractive platform for vaccine development as a result of the ability to induce persistent humoral- and cellular-mediated immune responses against the encoded transgene. Compared with the parental integrating vector, the main advantages for using IDLV are the reduced hazard of insertional mutagenesis and the decreased risk for vector mobilization by wild-type viruses. Here we report on the development and use in the mouse immunogenicity model of simian immunodeficiency virus (SIV)-based IDLV containing a long deletion in the U3 region and with the 3' polypurine tract (PPT) removed from the transfer vector for improving safety and/or efficacy. Results show that a safer extended deletion of U3 sequences did not modify integrase-mediated or -independent integration efficiency. Interestingly, 3' PPT deletion impaired integrase-mediated integration but did not reduce illegitimate, integrase-independent integration efficiency, contrary to what was previously reported in the HIV system. Importantly, although the extended deletion in the U3 did not affect expression or immunogenicity from IDLV, deletion of 3' PPT considerably reduced both expression and immunogenicity of IDLV.

Duke Scholars

Published In

Mol Ther Methods Clin Dev

DOI

ISSN

2329-0501

Publication Date

December 10, 2021

Volume

23

Start / End Page

263 / 275

Location

United States

Related Subject Headings

  • 3206 Medical biotechnology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bona, R., Michelini, Z., Mazzei, C., Gallinaro, A., Canitano, A., Borghi, M., … Cara, A. (2021). Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization. Mol Ther Methods Clin Dev, 23, 263–275. https://doi.org/10.1016/j.omtm.2021.09.011
Bona, Roberta, Zuleika Michelini, Chiara Mazzei, Alessandra Gallinaro, Andrea Canitano, Martina Borghi, Maria Fenicia Vescio, et al. “Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.Mol Ther Methods Clin Dev 23 (December 10, 2021): 263–75. https://doi.org/10.1016/j.omtm.2021.09.011.
Bona R, Michelini Z, Mazzei C, Gallinaro A, Canitano A, Borghi M, et al. Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization. Mol Ther Methods Clin Dev. 2021 Dec 10;23:263–75.
Bona, Roberta, et al. “Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.Mol Ther Methods Clin Dev, vol. 23, Dec. 2021, pp. 263–75. Pubmed, doi:10.1016/j.omtm.2021.09.011.
Bona R, Michelini Z, Mazzei C, Gallinaro A, Canitano A, Borghi M, Vescio MF, Di Virgilio A, Pirillo MF, Klotman ME, Negri D, Cara A. Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization. Mol Ther Methods Clin Dev. 2021 Dec 10;23:263–275.
Journal cover image

Published In

Mol Ther Methods Clin Dev

DOI

ISSN

2329-0501

Publication Date

December 10, 2021

Volume

23

Start / End Page

263 / 275

Location

United States

Related Subject Headings

  • 3206 Medical biotechnology