Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Developing the IVIG biomimetic, Hexa-Fc, for drug and vaccine applications

Tools
- Tools
+ Tools

Czajkowsky, Daniel M., Andersen, J. T., Fuchs, Anne, Wilson, T. J., Mekhaie, D., Colonna, M., He, J., Shao, Zhiyuan, Mitchell, Daniel A., Wu, Gang, Dell, Anne, Haslam, S., Lloyd, K. A., Moore, Stephen J., Sandlie, I., Blundell, P. A. and Richard, J. P. (2015) Developing the IVIG biomimetic, Hexa-Fc, for drug and vaccine applications. Scientific Reports, Volume 5 . Article number 5926. doi:10.1038/srep09526 ISSN 2045-2322.

Research output not available from this repository.

Request-a-Copy directly from author or use local Library Get it For Me service.

Official URL: http://dx.doi.org/10.1038/srep09526

Request Changes to record.

Abstract

The remarkable clinical success of Fc-fusion proteins has driven intense investigation for even more potent replacements. Using quality-by-design (QbD) approaches, we generated hexameric-Fc (hexa-Fc), a ~20 nm oligomeric Fc-based scaffold that we here show binds low-affinity inhibitory receptors (FcRL5, FcγRIIb, and DC-SIGN) with high avidity and specificity, whilst eliminating significant clinical limitations of monomeric Fc-fusions for vaccine and/or cancer therapies, in particular their poor ability to activate complement. Mass spectroscopy of hexa-Fc reveals high-mannose, low-sialic acid content, suggesting that interactions with these receptors are influenced by the mannose-containing Fc. Molecular dynamics (MD) simulations provides insight into the mechanisms of hexa-Fc interaction with these receptors and reveals an unexpected orientation of high-mannose glycans on the human Fc that provides greater accessibility to potential binding partners. Finally, we show that this biosynthetic nanoparticle can be engineered to enhance interactions with the human neonatal Fc receptor (FcRn) without loss of the oligomeric structure, a crucial modification for these molecules in therapy and/or vaccine strategies where a long plasma half-life is critical.

Item Type: Journal Article
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
Q Science > QR Microbiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Immunological adjuvants, Molecules--Models , Vaccines
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
Official Date: 27 April 2015
Dates:
DateEvent
27 April 2015Published
26 February 2015Accepted
29 October 2014Submitted
Volume: Volume 5
Number of Pages: 11
Article Number: Article number 5926
DOI: 10.1038/srep09526
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Funder: Royal Society (Great Britain), Medical Research Council (Great Britain) (MRC), Baxter International Inc., Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Guo jia zi ran ke xue ji jin wei yuan hui (China) [National Natural Science Foundation of China] (NSFC), Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST), Norges forskningsråd [Norwegian Research Council], Norway. Helse- og omsorgsdepartementet‏ [Ministry of Health and Care Services]
Grant number: BT11-000280 (Baxter), 91129000 (NSFC), 11374207 (NSFC), 31370750 (NSFC), 21303104 (NSFC), 2010CB529205 (MOST), 179573 (Norwegian Research Council, 230526/F20 ((Norwegian Research Council), 179573/V40 (Norwegian Research Council), 39375 (Norway. Helse- og

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item
twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us