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Toward reducing biomaterial antigenic potential: a miniaturized Fc-binding domain for local deposition of antibodies

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Abstract

A peptide derived from staphylococcal protein A (SpA) was developed as an affinity module for antibody delivery applications. The miniaturized protein consists of the first helix of the engineered SpA Z domain fused with the self-assembling peptide (SAP) AEAEAKAKAEAEAKAK, or EAK. The resulting peptide, named Z15_EAK, was shown to possess fibrillization properties and an Fc-binding function. The peptide induced a red shift in the Congo red absorbance characteristic of peptide fibrils, also evidenced in transmission electron microscopy images. The one-site binding affinity (Kd) of a gel-like coacervate generated by admixing Z15_EAK with EAK for IgG was determined to be 1.27 ± 0.14 μM based on a microplate-based titration assay. The coacervate was found to localize IgG subcutaneously in mouse footpads for 8 to 28 days. A set of in vivo data was fit to a one-compartment model for simulating the relative fractions of IgG dissociated from the materials in the depot. The model predicted that close to 27% of the antibodies injected were available unbound for the duration of the experiment. Z15_EAK did not appear to induce innate immune responses; injecting Z15_EAK into mouse footpads elicited neither interleukin-6 (IL-6) nor tumor necrosis factor-alpha (TNF-α) from splenocytes isolated from the animals one day, seven days, or eleven days afterward. The antigenic potential of Z15 was analyzed using a bioinformatic approach in predicting sequences in SpA and Z15 dually presented by class I and class II human MHC alleles covering the majority of the population. A peptide in SpA identified as a potential T cell epitope cross reacting with a known epitope in a microbial antigen was eliminated by miniaturization. These results demonstrate that Z15_EAK is a potential platform for generating antibody depots by which the impacts of Fc-based biotherapeutics can be enhanced through spatiotemporal control.

Graphical abstract: Toward reducing biomaterial antigenic potential: a miniaturized Fc-binding domain for local deposition of antibodies

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Publication details

The article was received on 01 Oct 2018, accepted on 03 Dec 2018 and first published on 21 Dec 2018


Article type: Paper
DOI: 10.1039/C8BM01220B
Citation: Biomater. Sci., 2019, Advance Article
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    Toward reducing biomaterial antigenic potential: a miniaturized Fc-binding domain for local deposition of antibodies

    N. B. Pham, W. Liu, N. R. Schueller, E. S. Gawalt, Y. Fan and W. S. Meng, Biomater. Sci., 2019, Advance Article , DOI: 10.1039/C8BM01220B

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