Designing string-of-beads vaccines with optimal spacers

Genome Medicine
Benjamin Schubert, Oliver Kohlbacher

Abstract

String-of-beads polypeptides allow convenient delivery of epitope-based vaccines. The success of a polypeptide relies on efficient processing: constituent epitopes need to be recovered while avoiding neo-epitopes from epitope junctions. Spacers between epitopes are employed to ensure this, but spacer selection is non-trivial.We present a framework to determine optimally the length and sequence of a spacer through multi-objective optimization for human leukocyte antigen class I restricted polypeptides. The method yields string-of-bead vaccines with flexible spacer lengths that increase the predicted epitope recovery rate fivefold while reducing the immunogenicity from neo-epitopes by 44% compared to designs without spacers.

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Citations

Oct 30, 2016·Bioinformatics·Qamar M SheikhDarren R Flower
May 10, 2017·BMC Bioinformatics·Benjamin SchubertOliver Kohlbacher
Jun 23, 2018·Chemical Biology & Drug Design·David MurphyDarren R Flower
May 19, 2019·Nature Protocols·Muhammad AliJohanna Olweus
Aug 9, 2020·Scientific Reports·Florian BourdeauxMartin Grininger
Mar 13, 2020·ImmunoTargets and Therapy·Angus Nnamdi OliGordon C Ibeanu
Dec 12, 2019·Frontiers in Immunology·Lucas Michel-TodóJulio Alonso-Padilla
Oct 24, 2020·PLoS Computational Biology·Emilio Dorigatti, Benjamin Schubert
Nov 24, 2020·Journal of Biomolecular Structure & Dynamics·Sergei I BazhanLarisa I Karpenko
Jan 1, 2021·Bioinformatics·Emilio Dorigatti, Benjamin Schubert
Feb 25, 2021·Advances and Applications in Bioinformatics and Chemistry : AABC·Raquel Robleda-CastilloJulio Alonso-Padilla
Aug 25, 2020·Physics Reports·Ernesto Estrada
Jun 3, 2021·Expert Opinion on Drug Discovery·Fabio BonioloMichael P Menden

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Software Mentioned

SMM
SMMPMBEC
NetMHC
SYFPEITHI
EpiToolKit
Pyomo
Python
R
ProteaSMM
PCM

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