In silico and in vitro immunogenicity assessment of B-domain-modified recombinant factor VIII molecules

Haemophilia : the Official Journal of the World Federation of Hemophilia
C BartholdyKasper Lamberth

Abstract

B-domain modification can improve production of recombinant factor VIII (rFVIII) proteins. However, the engineered junction results in non-native peptide sequences with the potential to elicit immune responses via major histocompatibility complex class-II (MHC-II)-binding and CD4+ T cell activation. Assess the immunogenic potential of B-domain junction peptides of turoctocog alfa and other B-domain-modified rFVIII proteins using in silico and in vitro immunogenicity assessment techniques. Peptides with amino acid sequences identical to the B-domain junction of turoctocog alfa, simoctocog alfa and moroctocog alfa were evaluated by in silico peptide-MHC-II binding prediction, in vitro peptide-MHC-II-binding measurement and in vitro T cell-activation assays. Moreover, turoctocog alfa was assessed for peptide presentation on dendritic cells (DCs) using MHC-associated peptide proteomics. In silico analysis predicted virtually no neo-epitopes in the B-domain junction for turoctocog alfa, whereas some were predicted for simoctocog alfa and moroctocog alfa. Turoctocog alfa and moroctocog alfa peptides showed minimal capacity to bind high-frequency MHC-II molecules in vitro, whereas simoctocog alfa peptide demonstrated some degree of bi...Continue Reading

References

Dec 26, 2001·Bioinformatics·H Singh, G P Raghava
Feb 12, 2004·Seminars in Hematology·Johannes OldenburgEdward Tuddenham
Sep 11, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·W S BrilJ Voorberg
Sep 29, 2004·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Tim D JonesMatthew P Baker
May 5, 2005·Journal of Thrombosis and Haemostasis : JTH·T D JonesM P Baker
Jul 8, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew M ScottLloyd J Old
Nov 23, 2006·Journal of Pharmaceutical and Biomedical Analysis·Amer Jaber, Matthew Baker
Jan 6, 2009·BMC Bioinformatics·Hong Huang LinVladimir Brusic
Nov 13, 2009·Haemophilia : the Official Journal of the World Federation of Hemophilia·L ThimT D Steenstrup
May 20, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·D Green
Jan 10, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Leonard MoiseDavid W Scott
Dec 5, 2012·Journal of Thrombosis and Haemostasis : JTH·R T PetersG F Pierce
Jan 18, 2013·The New England Journal of Medicine·Samantha C GouwUNKNOWN PedNet and RODIN Study Group
Aug 9, 2013·Blood·Corien L EckhardtUNKNOWN INSIGHT Study Group
Sep 26, 2013·Trends in Pharmacological Sciences·Chava Kimchi-SarfatyZuben E Sauna
Aug 27, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·K M LövgrenB Wiinberg
Oct 21, 2017·Therapeutic Advances in Hematology·Lorraine A Cafuir, Christine L Kempton

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Citations

Mar 11, 2020·Expert Review of Hematology·Ana Boban, Cedric Hermans
Mar 23, 2021·The FEBS Journal·Martin A RossottiJamshid Tanha

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