The VirG functional epitopes identified from this study, together with the functional epitopes from IpaB and IpaD identified empirically in previous studies (38, 39), and Shiga toxins (unpublished data), enable us to construct an optimal epitope- and structure-based Shigella MEFA protein to induce broadly protective antibodies against the key Shigella virulence determinants and develop a cross-protective vaccine against shigellosis. Here, VIPR1 is linked to shigellosis.