New Approaches to in silico Design of Epitope-Based Vaccines

Chapter 7
Applications
In the previous chapters we have proposed new approaches to the in silico design of EVs.
This chapter focuses on applications of some of these methods. We begin with introducing
OptiTope, a publicly available and easy-to-use web server that we developed to make
our mathematical framework for epitope selection (Chapter 5) available to immunologists.
Subsequently, we will present two vaccine design studies. The first study focuses on the
design of a peptide cocktail vaccine against HCV. In the second study we employed our
algorithms to analyze the feasibility of designing string-of-beads vaccines against highly
variable viruses like HIV, HCV and IV yielding broad coverage of the targeted population
as well as of the various viral strains. Parts of this chapter have previously been
published [102, 103].
7.1 OptiTope – A Web Server for Epitope Selection
Based on a specific application of our epitope selection framework, OptiTope aims at assisting
immunologists in the critical task of epitope selection. It is an easy-to-use web-based
tool to efficiently determine an optimal set of epitopes in a specific individual or a target
population.
7.1.1 Web Interface
OptiTope requires the following input data: (1) sequences of known antigens, (2) a target
population, i.e., MHC alleles and corresponding probabilities and (3) the user’s requirements
on the epitope set to be selected. The information given by the user is transformed
into an optimization problem. If this problem is feasible, OptiTope will return an optimal
set of epitopes along with additional information on their respective contribution to the
overall immunogenicity. Otherwise, OptiTope will propose changes to the user’s requirements
that might yield a feasible optimization problem. The structure of the web interface
is depicted in Figure 7.1.
An introductory tutorial is provided on the OptiTope home page to assist new users in
learning how to use the web server.
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