Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro

Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administ...

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Bibliographic Details
Published in:Journal of virological methods 2005-06, Vol.126 (1), p.31-36
Main Authors: Steel, Jason C., Cavanagh, Heather M.A., Burton, Mark A., Dingwall, Daniel J., Kalle, Wouter H.J.
Format: Article
Language:English
Subjects:
Adenoviridae - chemistry
Adenoviridae - immunology
Adenovirus
AL complexes
beta-Galactosidase - genetics
beta-Galactosidase - metabolism
Biological and medical sciences
Cell Line
Fundamental and applied biological sciences. Psychology
Gene Expression
Genes, Reporter
Genetic Vectors - chemistry
Genetic Vectors - immunology
Humans
Immuno-protection
Liposomes
Liposomes - chemistry
Liposomes - immunology
Liposomes - toxicity
Microbiology
Neutralising antibodies
Neutralization Tests
Phosphatidylethanolamines - chemistry
Phosphatidylethanolamines - immunology
Quaternary Ammonium Compounds - chemistry
Quaternary Ammonium Compounds - immunology
Techniques used in virology
Virology
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Summary:Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)–dioleoyl- l-phosphatidylethanolamine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes’ ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral–liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels.
ISSN:0166-0934
1879-0984
DOI:10.1016/j.jviromet.2005.01.017