Epitope mutant VLPs were compared to wild type strain VLPs for reactivity to the donor plasma sample. Consistent with high EIA reactivity to GII.4.1987 and 2006 VLPs (Table 2 and Figure  S2 ), donor plasma reacted across the panel of epitope-exchange mutant VLPs ( Figure 10B) . Donor plasma was able to block each epitope-exchanged VLP binding to PGM ( Figure 11A and C) . Exchange of all of the epitopes, except Epitope D into either backbone and GII.4.1987 C into GII.4.2006 resulted in significantly different EC50 values compared to the parental strains ( Figure 11B , 11D, and Table S4 ) (p,0.05). Only the exchange of Epitope A between the backbones resulted in an exchanged blockade phenotype, as observed with epitope-specific mAbs [43] . Exchange of Epitope A between the two parental backbones resulted in a chimeric VLP (GII.4.1987/2006A) that was blocked with significantly less plasma than the parental GII.4.1987 (EC50 0.0167 mg/ml compared to 0.0673 mg/ml) (p,0.05) and a chimeric VLP (GII.4.2006/1987A) that was blocked with signif- Figure S2 and Table 2 ). Bars are SEM. doi:10.1371/journal.ppat.1002705.g008 Table S4 ) (p,0.05). In this individual, these data suggest that Epitope A may be an important evolving GII.4 neutralization epitope as the blockade response is significant enough to be detected in the polyclonal antibody response.