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Hum Gene Ther. 2011 Sep;22(9):1083-94. doi: 10.1089/hum.2010.218. Epub 2011 Apr 18.

Use of DAF-displaying adenovirus vectors reduces induction of transgene- and vector-specific adaptive immune responses in mice.

Author information

1
Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, USA.

Abstract

Adenovirus (Ad)-based vectors are attractive candidates for a variety of gene-transfer applications. In this study, we found that decay-accelerating factor (DAF)-displaying Ads induce significantly decreased cellular immune responses to transgenes expressed from the vectors in both Ad5-naive and Ad5-immune mice. Specifically, we found a diminished ability of splenocytes to secrete interferon-γ after recall exposure to multiple peptides derived from antigens expressed by DAF-displaying Ads. We also confirmed that DAF-displaying Ads induce decreased numbers of antigen-specific, CD8(+) effector memory and central memory CD8(+) T cells, thereby uncovering a unique role of complement in modulating the induction of robust memory T-cell responses. We also confirmed that DAF-displaying Ads generate significantly reduced titers of Ad capsid-specific neutralizing antibodies after gene transfer in vivo. In conclusion, DAF-displaying Ad5-based vectors exhibit decreased induction of complement-dependent, innate immune responses, resulting in both an improved safety profile and a decreased propensity to induce humoral and cellular adaptive immune responses to Ad capsid proteins and Ad vector-expressed transgene products. This attractive combination of features will be beneficial in a variety of clinically relevant gene-transfer applications.

PMID:
21388344
PMCID:
PMC3177950
DOI:
10.1089/hum.2010.218
[Indexed for MEDLINE]
Free PMC Article

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