A major hurdle in vaccine development is the difficulty in identifying relevant 
target epitopes and then presenting them to the immune system in a context that 
mimics their native conformation. We have engineered novel virus-like-particle 
(VLP) technology that is able to display complex libraries of random peptide 
sequences on a surface-exposed loop in the coat protein without disruption of 
protein folding or VLP assembly. This technology allows us to use the same VLP 
particle for both affinity selection and immunization, integrating the power of 
epitope discovery and epitope mimicry of traditional phage display with the high 
immunogenicity of VLPs. Previously, we showed that using affinity selection with 
our VLP platform identifies linear epitopes of monoclonal antibodies and 
subsequent immunization generates the proper antibody response. To test if our 
technology could identify immunologic mimotopes, we used affinity selection on a 
monoclonal antibody (AP4-24H11) that recognizes the Staphylococcus aureus 
autoinducing peptide 4 (AIP4). AIP4 is a secreted eight amino acid, cyclized 
peptide produced from the S. aureus accessory gene regulator (agrIV) 
quorum-sensing operon. The agr system coordinates density dependent changes in 
gene expression, leading to the upregulation of a host of virulence factors, and 
passive transfer of AP4-24H11 protects against S. aureus agrIV-dependent 
pathogenicity. In this report, we identified a set of peptides displayed on VLPs 
that bound with high specificity to AP4-24H11. Importantly, similar to passive 
transfer with AP4-24H11, immunization with a subset of these VLPs protected 
against pathogenicity in a mouse model of S. aureus dermonecrosis. These data 
are proof of principle that by performing affinity selection on neutralizing 
antibodies, our VLP technology can identify peptide mimics of non-linear 
epitopes and that these mimotope based VLP vaccines provide protection against 
pathogens in relevant animal models.