Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients
Ahmed S. Fahad, Morgan R. Timm, Bharat Madan, Katherine E. Burgomaster, Kimberly A. Dowd, Erica Normandin, Matías Gutiérrez-González, Joseph M. Pennington, Matheus Oliveira de Souza, Amy R. Henry, Farida Laboune, Lingshu Wang, David R. Ambrozak, Ingelise J. Gordon, Daniel C. Douek, Julie E. Ledgerwood, Barney S. Graham, Leda R. Castilho, Theodore C. Pierson, John R. Mascola, Brandon J. DeKosky
Abstract
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.