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

Overview of attention for article published in Scientific Reports, April 2015
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  • Good Attention Score compared to outputs of the same age (71st percentile)
  • Good Attention Score compared to outputs of the same age and source (68th percentile)

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Citations

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33 Dimensions

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Title
Developing the IVIG biomimetic, Hexa-Fc, for drug and vaccine applications
Published in
Scientific Reports, April 2015
DOI 10.1038/srep09526
Pubmed ID
Authors

Daniel M. Czajkowsky, Jan Terje Andersen, Anja Fuchs, Timothy J. Wilson, David Mekhaiel, Marco Colonna, Jianfeng He, Zhifeng Shao, Daniel A. Mitchell, Gang Wu, Anne Dell, Stuart Haslam, Katy A. Lloyd, Shona C. Moore, Inger Sandlie, Patricia A. Blundell, Richard J. Pleass

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.

X Demographics

X Demographics

The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 63 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
Unknown 62 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 27 43%
Researcher 10 16%
Student > Master 7 11%
Student > Bachelor 3 5%
Professor 3 5%
Other 7 11%
Unknown 6 10%
Readers by discipline Count As %
Immunology and Microbiology 17 27%
Agricultural and Biological Sciences 13 21%
Medicine and Dentistry 8 13%
Biochemistry, Genetics and Molecular Biology 7 11%
Chemistry 3 5%
Other 6 10%
Unknown 9 14%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 March 2016.
All research outputs
#6,505,161
of 23,511,526 outputs
Outputs from Scientific Reports
#44,381
of 127,160 outputs
Outputs of similar age
#75,759
of 266,579 outputs
Outputs of similar age from Scientific Reports
#452
of 1,416 outputs
Altmetric has tracked 23,511,526 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 127,160 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.3. This one has gotten more attention than average, scoring higher than 65% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 266,579 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 71% of its contemporaries.
We're also able to compare this research output to 1,416 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.