Simian immunodeficiency virus-Vpx for improving integrase defective lentiviral vector-based vaccines.
BACKGROUND
Integrase defective lentiviral vectors (IDLV) represent a promising delivery system for immunization purposes. Human dendritic cells (DC) are the main cell types mediating the immune response and are readily transduced by IDLV, allowing effective triggering of in vitro expansion of antigen-specific primed CD8+ T cells. However, IDLV expression in transduced DC is at lower levels than those of the integrase (IN) competent counterpart, thus requiring further improvement of IDLV for future use in the clinic.


RESULTS
In this paper we show that the addition of simian immunodeficiency (SIV)-Vpx protein in the vector preparation greatly improves transduction of human and simian DC, but not of murine DC, thus increasing the ability of transduced DC to act as functional antigen presenting cells, in the absence of integrated vector sequences. Importantly, the presence of SIV-Vpx allows for using lower dose of input IDLV during in vitro transduction, thus further improving the IDLV safety profile.


CONCLUSIONS
These results have significant implications for the development of IDLV-based vaccines.
Department of Infectious, Parasitic and Immune-mediated Diseases, Viale Regina Elena 299, Rome 00161, Italy. donatella.negri@iss.it
Donatella R M
DR
Negri
Alessandra
A
Rossi
Maria
M
Blasi
Zuleika
Z
Michelini
Pasqualina
P
Leone
Maria Vincenza
MV
Chiantore
Silvia
S
Baroncelli
Gemma
G
Perretta
Andrea
A
Cimarelli
Mary E
ME
Klotman
Andrea
A
Cara
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D014161:Transduction, Genetic; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics*; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology*
C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D014765:Viral Vaccines