Unknown

Dataset Information

0

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


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-? 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.

SUBMITTER: Seregin SS 

PROVIDER: S-EPMC3177950 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Seregin Sergey S SS   Aldhamen Yasser A YA   Appledorn Daniel M DM   Zehnder Jennifer J   Voss Tyler T   Godbehere Sarah S   Amalfitano Andrea A  

Human gene therapy 20110418 9


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 al  ...[more]

Similar Datasets

| S-EPMC2947391 | biostudies-literature
| S-EPMC2895756 | biostudies-literature
| S-EPMC4331283 | biostudies-literature
| S-EPMC415814 | biostudies-other
| S-EPMC4981243 | biostudies-literature
| S-EPMC3149177 | biostudies-literature
| S-EPMC1346928 | biostudies-literature
| S-EPMC5378976 | biostudies-literature
| S-EPMC4424821 | biostudies-other
| S-EPMC2865218 | biostudies-literature