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A lentiviral vector pseudotype suitable for vaccine development
Author(s) -
Lopes Luciene,
Dewannieux Marie,
Takeuchi Yasuhiro,
Collins Mary K.
Publication year - 2011
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1553
Subject(s) - vesicular stomatitis virus , virology , viral vector , ross river virus , biology , immune system , cell culture , cytotoxic t cell , virus , immunology , in vitro , recombinant dna , alphavirus , gene , genetics
Background Lentiviral vectors (LV) are promising vaccines because they transduce dendritic cells (DC) in vivo . To translate LV vaccines into clinical trials, bulk production will be necessary. The present study aimed to find a suitable envelope for LV vaccine production from stable packaging cells because the commonly used vesicular stomatitis virus envelope (VSV‐G) is cytotoxic. Methods The envelope from Ross river virus (RRV) was selected. It can infect mouse and human cells, allowing testing in animals before clinical translation. We used VSV‐G for comparison. Vectors produced with each envelope were titred on human 293T cells and mouse 3T3 cells. Results RRV‐pseudotyped LV (RRV‐LV) infected mouse myeloid DC in culture and immunized mice. An approximately 50‐fold higher dose of RRV‐LV than VSV‐G‐LV was required to generate a similar T cell response. The RRV‐LV could also be used to infect human mDC and to prime a human T cell immune response. Conclusions RRV envelope is a suitable candidate to be used for the construction of an LV producer cell line. LV vaccines with RRV envelope can be tested in mice and in human immune cell cultures. The higher dose of RRV‐LV required for vaccine efficacy compared to VSV‐G‐LV will partly be offset by ease of production. Copyright © 2011 John Wiley & Sons, Ltd.