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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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 Date

  • December 10, 2021

Published In

Volume / Issue

  • 23 /

Start / End Page

  • 263 - 275

PubMed ID

  • 34729374

Pubmed Central ID

  • PMC8526422

International Standard Serial Number (ISSN)

  • 2329-0501

Digital Object Identifier (DOI)

  • 10.1016/j.omtm.2021.09.011

Language

  • eng

Conference Location

  • United States