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BRIEF RESEARCH REPORT article
Front. Bioeng. Biotechnol.
Sec. Biomaterials
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1558627
Rational design of FVIII sialylated peptides to target Siglec-3 and Siglec-9 and improve peptide formulations for reverse vaccines
Provisionally accepted
Eleonora Nardini 1,2
Brigitte-Carole Keumatio Doungtsop 1,2
Tania Gerpe-Amor 3
Aram M. de Haas 1,2
Mike De Kok 1 Evert Peterse 4 Hakan Kalay 1
Rui-Jún Eveline Li 1,4
Fabrizio Chiodo 1,2,5
Alba Silipo 3 Jan Voorberg 6
Yvette Van Kooyk 1,2*- 1 Amsterdam University Medical Center, Amsterdam, Netherlands
- 2 Amsterdam Institute for Infection and Immunity, VU Medical Center, Amsterdam, Netherlands
- 3 Department of Chemical Sciences and Task Force for Microbiome Studies, University of Naples Federico II, Naples, Campania, Italy
- 4 AmbroSia, Amsterdam, Netherlands
- 5 Institute of Biomolecular Chemistry, Department of Chemical Sciences and Materials Technologies, National Research Council (CNR), Pozzuoli, Campania, Italy
- 6 Department of Molecular Hematology, Sanquin Research, Amsterdam, Netherlands
Reverse vaccine formulations have shown their potential for the treatment of allergies and other autoimmune diseases by the design of antigens that modify dendritic cell (DC) function towards tolerogenic responses. We here demonstrate that modification of an immunodominant peptide from factor VIII (FVIII) with a tolerizing molecule, sialic acid, improves existing peptide formulations towards the induction of tolerogenic cytokine secretion by DCs.Sialic acids are the end-standing moiety of mammalian N-and O-glycans, which are naturally recognized as self-associated molecular pattern. In this paper we show that sialic acid modified FVIII peptides target Siglec-3 and -9 on DCs and increase IL-10 secretion. Our work proposes a method to select, synthetize and test sialylated immunodominant peptides with the aim of ameliorating the efficacy of peptide immunotherapy. Based on our results, we propose that the sialylated FVIII peptide designed in this study may be useful for re-establishing tolerance to FVIII in hemophilia A patients who developed neutralizing antibodies following treatment.
Keywords: Hemophilia A, FVIII, inhibitors, sialic acid, Siglec-9, Peptide immunotherapy, tolerance, Dendritic Cells
Received: 10 Jan 2025; Accepted: 21 Mar 2025.
Copyright: © 2025 Nardini, Keumatio Doungtsop, Gerpe-Amor, de Haas, De Kok, Peterse, Kalay, Li, Chiodo, Silipo, Voorberg and Van Kooyk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yvette Van Kooyk, Amsterdam University Medical Center, Amsterdam, Netherlands
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