The described mAbs indicate at least five unique or overlapping GII.4 blockade epitopes with different specificities: 1) early GII.4 strain specific, 2) contemporary GII.4 strain specific, 3) Minervavariant strain specific, 4) genogroup II strain specific, and 5) GII.4 strain specific. Using capsid sequences as a guide, mutant VLPs were designed to contain chimeric combinations of the predicted evolving GII.4 epitopes ( Figure 10) All epitope exchange VLPs were morphologically intact by electron microscopy visualization and retained the ability to bind PGM ( Figure 10A and B, [43] ), confirming chimeric VLP structural integrity.