Large-scale analysis of B-cell epitopes of envelope: Implications for Zika vaccine and immunotherapeutic development.

Cases of the re-emergence of Zika virus in 2015 were associated with severe neurologic complications, including Gillien-Barre syndrome in adults and congenital Zika syndrome in newborns. The major structural determinant of immunity to the Zika virus is the E protein. Although B-cell epitopes of Zika E protein were recently identified, data regarding epitope variations among Zika strains in pre-epidemic and epidemic periods are lacking. Here, we conducted systematic bioinformatics analyses of Zika strains isolated between 1968 and 2017. Multiple sequence alignment of E protein as well as B-cell epitopes annotations were performed. In addition, homology-based approach was utilized to construct three-dimensional structures of monomeric E glycoproteins to annotate epitope variations. Lastly, prediction of of -glycosylation patterns and prediction of protein stability upon mutations were also investigated. Our analyses indicates that epitopes recognized by human mAbs ZIKV-117, ZIKV-15, and ZIKV-19 were highly conserved, suggesting as attractive targets for the development of vaccines and immunotherapeutics directed against diverse Zika strains. In addition, the epitope recognized by ZIKV-E-2A10G6 mAb derived from immunized mice was mostly conserved across Zika strains. Our data provide new insights regarding antigenic similarities between Zika strains circulating worldwide. These data are essential for understanding the impact of evolution on antigenic cross-reactivity between Zika lineages and strains. Further analyses are needed to determine how mutationsat predefined epitopes could impact the development of vaccines that can effectively neutralize Zika viruses.