Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.
HIV
LTR
SIV
episomal DNA
human immunodeficiency virus
immunization
integrase
lentiviral vector
simian immunodeficiency virus
vaccine
Journal
Molecular therapy. Methods & clinical development
ISSN: 2329-0501
Titre abrégé: Mol Ther Methods Clin Dev
Pays: United States
ID NLM: 101624857
Informations de publication
Date de publication:
10 Dec 2021
10 Dec 2021
Historique:
received:
27
04
2021
accepted:
24
09
2021
entrez:
3
11
2021
pubmed:
4
11
2021
medline:
4
11
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34729374
doi: 10.1016/j.omtm.2021.09.011
pii: S2329-0501(21)00149-2
pmc: PMC8526422
doi:
Types de publication
Journal Article
Langues
eng
Pagination
263-275Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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