Simian immunodeficiency virus-Vpx for improving integrase defective lentiviral vector-based vaccines

Retrovirology

Andrea Cara²  Mary E Klotman⁴  Andrea Cimarelli¹  Gemma Perretta³  Silvia Baroncelli²  Maria Vincenza Chiantore⁵  Pasqualina Leone²  Zuleika Michelini²  Maria Blasi⁴  Alessandra Rossi⁵  Donatella RM Negri⁵ 

[1] Department of Human Virology, Ecole Normale Supérieure de Lyon, Lyon, France;Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy;Istituto di Biologia Cellulare e Neurobiologia-CNR, c/o ENEA-Casaccia, Roma 00123, Italy;Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA;Department of Infectious, Parasitic and Immune-mediated Diseases, Viale Regina Elena 299, Rome 00161, Italy

关键词: Integrase;    Dendritic cells;    Vaccine;    Vpx;    Lentiviral vector;   

Others  :  1209273
DOI  :  10.1186/1742-4690-9-69

 received in 2011-12-09, accepted in 2012-08-07,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Negri et al.; licensee BioMed Central Ltd.

【 图 表 】

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