Graph-theoretical formulation of the generalized epitope-based vaccine design problem.

Roger Dimitri Kouyos,Emilio Dorigatti,Benjamin Schubert

doi:10.1371/journal.pcbi.1008237

Abstract

Epitope-based vaccines have revolutionized vaccine research in the last decades. Due to their complex nature, bioinformatics plays a pivotal role in their development. However, existing algorithms address only specific parts of the design process or are unable to provide formal guarantees on the quality of the solution. We present a unifying formalism of the general epitope vaccine design problem that tackles all phases of the design process simultaneously and combines all prevalent design principles. We then demonstrate how to formulate the developed formalism as an integer linear program, which guarantees optimality of the designs. This makes it possible to explore new regions of the vaccine design space, analyze the trade-offs between the design phases, and balance the many requirements of vaccines.

Highlights

In recent years, vaccines based on T-cell epitopes, so-called epitope-based vaccines (EV), have become wildly used as therapeutic treatments in case of cancer immunotherapy [1,2,3,4] and prophylactically against infectious diseases [5,6,7,8,9,10]
Current methods are lacking in one of several aspects, as they only focus on a specific part of the design problem, on a specific type of vaccine, or are unable to guarantee optimality of the solution
We present a new method to design vaccines that does not suffer from any of these limitations: through a holistic view on the design problem, it can find the best solution for the given design constraints

Summary

Introduction

Vaccines based on T-cell epitopes, so-called epitope-based vaccines (EV), have become wildly used as therapeutic treatments in case of cancer immunotherapy [1,2,3,4] and prophylactically against infectious diseases [5,6,7,8,9,10]. Compared to regular attenuated vaccines, EVs offer several advantages [11]. EVs do not bare the risk of reversion to virulence as they do not contain any infectious material, and the selection of epitopes can be tailored to address the genetic variability of a pathogen and that of a targeted population or individual increasing its potential efficacy [11]. Epitopes correctly recovered from the vaccine construct have a chance to bind to the major histocompatibility complex class I (MHC) and be presented on the surface of the cell via the cross-presentation pathway [12]. Naive CD8+ T-cells, recognizing such an epitope-MHC complex, are activated and start circulating, hunting for identical complexes on the surface of infected cells

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Conclusion