The re-emergence of Zika virus (ZIKV) caused widespread infections that were linked to Guillain-Barré syndrome in adults and congenital malformation in fetuses, and epidemiological data suggest that ZIKV infection can induce protective antibody responses. A more detailed understanding of anti-ZIKV antibody responses may lead to enhanced antibody discovery and improved vaccine designs against ZIKV and related flaviviruses. Here, we applied recently-invented library-scale antibody screening technologies to determine comprehensive functional molecular and genetic profiles of naturally elicited human anti-ZIKV antibodies in three convalescent individuals. We leveraged natively paired antibody yeast display and NGS to predict antibody cross-reactivities and coarse-grain antibody affinities, to perform in-depth immune profiling of IgM, IgG, and IgA antibody repertoires in peripheral blood, and to reveal virus maturation state-dependent antibody interactions. Repertoire-scale comparison of ZIKV VLP-specific and non-specific antibodies in the same individuals also showed that mean antibody somatic hypermutation levels were substantially influenced by donor-intrinsic characteristics. These data provide insights into antiviral antibody responses to ZIKV disease and outline systems-level strategies to track human antibody immune responses to emergent viral infections.
Fahad, A. S., Timm, M. R., Madan, B., Burgomaster, K. E., Dowd, K. A., Normandin, E., Gutiérrez-González, M. F., Pennington, J. M., De Souza, M. O., Henry, A. R., Laboune, F., Wang, L., Ambrozak, D. R., Gordon, I. J., Douek, D. C., Ledgerwood, J. E., Graham, B. S., Castilho, L. R., Pierson, T. C., Mascola, J. R., … DeKosky, B. J. (2021). Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients. Frontiers in immunology, 12, 615102. https://doi.org/10.3389/fimmu.2021.615102