Our humoral immune response is mediated by antibodies and triggered when antigens are detected through the binding of their B-cell epitopes to surface receptors of B lymphocytes.  Most B-cell epitopes are conformational, formed by non-contiguous amino acid residues brought together by complex folding of the antigen. However, a small fraction are linear epitopes that are simpler, linear stretches of amino acid residues. Linear B-cell epitopes are ideal candidates in aiding vaccine formulation since they can trigger an immune response without proper folding and complex 3D conformation requirements.  

Synthetic peptides containing B-cell epitopes administered to animals have shown to stimulate their immune system to secrete antibodies that recognize antigens from which these epitopes are derived.  Therefore, the use of multiple synthetic peptides in formulating a vaccine is a highly promising approach in the development of subunit vaccines. These peptide-based vaccines have many advantages, including being both safer and more cost effective than attenuated and inactivated vaccines.  Several peptide-based vaccines are currently under development for the prevention of infectious diseases such as malaria, influenza, and HIV.  However, to identify B-cell epitope candidates rapidly and efficiently remains a formidable challenge. 

Current identification strategies tend to involve the experimental detection of epitopes on a single protein, which are low throughput (one protein at a time) and require initial knowledge of the antigen and its sequence. High throughput strategies are available, but they require extensive use of synthetic biology and other time-consuming methodologies, e.g., library construction, peptide/protein array preparation and expression of proteins using non-native expression systems.

A more practical approach to characterize B-cell epitopes for peptide-based vaccine formulation would have to be simple, efficient, cost-effective and high throughput.   Researchers at LLNL have developed a shotgun immunoproteomic approach that can fulfil these requirements while also be broadly applicable to the identification of linear B-cell epitopes from any pathogen.