New Approaches to in silico Design of Epitope-Based Vaccines

Chapter 1
Introduction
Motivation
The development of vaccines and their subsequent large-scale prophylactic use was undoubtedly
one of the most important advancements in medicine. Vaccines make use of the
adaptive part of the human immune system to protect from infections as well as to fight
chronic diseases and cancer.
From the very beginning, the development of vaccines was a process largely driven
by experiment. Attenuation of pathogens turned out to be a very reliable route to new
vaccines. However, there are still many diseases for which no viable vaccine could be found,
HIV infection and cancer being among the most prominent examples. In these cases, the
rational design of vaccines based on a molecular understanding of immunity, shows great
promise. Rational vaccine design uses experimental and computational methods to identify
immunogenic substances, i.e., antigens, suited to form the basis of the vaccine. Given a set
of potential antigens, several options for the construction of a vaccine exist: the antigens
or parts thereof can be used, either as intact protein [1, 2] or as corresponding RNA or
DNA [3, 4]. Using only the smallest immunogenic regions of a protein antigen, the so-called
epitopes, is particularly appealing, as these epitope-based vaccines (EVs) have numerous
advantages over other types of vaccines: apart from the comparatively simple production
in a well-controlled process, EVs can be designed – at least in theory – to evoke an immune
response that is very specifically directed at highly immunogenic regions of antigens. This
design process can also take the immune system of the host into consideration, providing
the basis for a personalized therapy. It is thus hardly surprising that EVs have recently
gained a lot of attention. Several clinical studies with EVs were successful [5–7]. Various
commercial products have now entered clinical phase III trials, indicating that the first
EVs for humans can be expected to enter the market in the near future.
The process of designing an EV can be roughly divided into three steps: epitope discovery,
epitope selection and epitope assembly (Figure 1.1). In each of these steps, computational
methods can be employed to facilitate the work of immunologists and to assist
them in their decisions. This in silico-guided approach to EV design promises improved
vaccines at reduced development time and cost.
1