Erythrocyte-targeted immunomodulatory antigens enabled by in vivo selection of D-peptides

Loftis, A. R.; Zhang, G.; Backlund, C.; Quartararo, A. J.; Pishesha, N.; Schissel, C. K.; Garafola, D.; Loas, A.; Collier, R. J.; Ploegh, H.; Irvine, D. J.; Pentelute, B. L.

doi:10.1101/2020.07.15.203331

bioRxiv · 10.1101/2020.07.15.203331

Erythrocyte-targeted immunomodulatory antigens enabled by in vivo selection of D-peptides

Loftis, A. R.·Zhang, G.·Backlund, C.·Quartararo, A. J.·Pishesha, N.·Schissel, C. K.·Garafola, D.·Loas, A.·Collier, R. J.·Ploegh, H.·Irvine, D. J.·Pentelute, B. L.

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Abstract

Targeting of antigens to erythrocytes can be used to selectively mitigate their immunogenicity, but the methods to equip a variety of cargoes with erythrocyte-targeting properties are limited. Here we identified a D-peptide that targets murine erythrocytes and decreases anti-drug antibody responses when conjugated to the protective antigen from Bacillus anthracis, a protein of therapeutic interest. The D-peptide likewise decreases inflammatory anti-ovalbumin (OVA) CD8+ T cell responses when attached to a peptide antigen derived from OVA. To discover this targeting ligand, we leveraged mass spectrometry to decode a randomized D-peptide library selected in mice, extending the application of synthetic libraries to in vivo affinity selections.

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Loftis, A. R., Zhang, G., Backlund, C., Quartararo, A. J., Pishesha, N., Schissel, C. K., Garafola, D., Loas, A., Collier, R. J., Ploegh, H., Irvine, D. J., Pentelute, B. L.. 2020-07-15. Erythrocyte-targeted immunomodulatory antigens enabled by in vivo selection of D-peptides. https://doi.org/10.1101/2020.07.15.203331

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