Systems vaccinology and big data in the vaccine development chain

Raeven, René H. M.; van Riet, Elly; Meiring, Hugo D.; Metz, Bernard; Kersten, Gideon F. A.

Receptors, ligands, enzymes, hormones and even structural proteins detect foreign substances, determine the identity of cells and communicate messages between cells and tissues. Profiling the subset of proteins and peptides involved in the immune response (termed immunoproteomics) 19 is important to understand how vaccines work. During the last three decades, mass spectrometry (MS) -based proteomics has emerged as an essential tool to profile this immunoproteome in terms of protein identification, protein dynamics and protein-protein interactions. Hunt et al. 20 pioneered the MS-based analysis of immunogenic peptides presented by molecules of the major histocompatibility complex (MHC). Since then, many studies have profiled the human leucocyte antigen (HLA) ligand repertoire using immunoprecipitation techniques and subsequent MS-based ligand identification to find new antigen leads and to understand the concept of immunogenicity. Apart from targeting infectious diseases, [21] [22] [23] [24] MHC ligandome analysis also is applied in, for example, cancer immunotherapy. 25 Recent studies, however, have shown that the plethora of MHC-presented peptides is even more complex than expected, due to the formation of non-linear peptide sequences (i.e. splicing variants) of these T-cell epitopes as it is estimated that one-third of the CD8 + T-cell epitopes is comprised of proteasome-generated spliced epitopes. [26] [27] [28] [29] In addition to profiling the T-cell epitope repertoire, assessing the antigenic determinants that interact with B-cells and antibodies is of high significance in elucidating immune responses in vaccine development and vaccine design. [30] [31] [32] Since B-cell epitopes are often conformational or even discontinuous, their identification is complex and currently not possible using in silico tools. With instrumental improvement of MS and the supporting software tools, MS is now used as a versatile tool to determine B-cell epitopes, that is, the areas where antibodies bind. Opuni et al. 33 comprehensively reviewed MS-based approaches to map B-cell epitopes. Antibody-antigen binding is just one example of a protein-protein interaction. Large-scale interaction analysis (interactomics) is rapidly developing to identify any type of protein-protein interaction.