Journal
JOURNAL OF CONTROLLED RELEASE
Volume 237, Issue -, Pages 78-88Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2016.07.004
Keywords
Adenovirus; Albumin; Albumin-binding domain; Neutralizing antibodies
Funding
- IDIBELL grant
- Ministerio de Economia y Competitividad of Spain [BIO2011-30299-C02-01, BIO2014-57716-C2-1-R]
- EU [29002 FP7-PEOPLE-2011-ITN]
- Generalitat de Catalunya [2014SGR364]
- [BFU2013-41249-P]
Ask authors/readers for more resources
Recombinant adenoviruses are used as vaccines, gene therapy vectors, and oncolytic viruses. However, the efficacy of such therapies is limited by pre-existing neutralizing antibodies (NAbs), especially when the virus is administered systemically for a wider biodistribution or to reach multiple metastases. To protect adenovirus against NAbs we inserted an albumin-binding domain (ABD) in the main adenovirus capsid protein, the hexon. This domain binds serum albumin to shield the virus upon systemic administration. The ABD-modified adenoviruses bind human and mouse albumin and maintain the infectivity and replication capacity in presence of NAbs. In pre-immunized mice non-modified viruses are completely neutralized, whereas ABD-modified viruses preserve the ability to transduce target organs, induce oncolysis, or generate immune responses to expressed proteins. Our results indicate that albumin coating of the virus capsid represents an effective approach to evade pre-existing NAbs. This strategy has translational relevance in the use of adenovirus for gene therapy, cancer virotherapy, and vaccination. (C) 2016 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available