AUTHOR=Fahad Ahmed S. , Timm Morgan R. , Madan Bharat , Burgomaster Katherine E. , Dowd Kimberly A. , Normandin Erica , Gutiérrez-González Matías F. , Pennington Joseph M. , De Souza Matheus Oliveira , Henry Amy R. , Laboune Farida , Wang Lingshu , Ambrozak David R. , Gordon Ingelise J. , Douek Daniel C. , Ledgerwood Julie E. , Graham Barney S. , Castilho Leda R. , Pierson Theodore C. , Mascola John R. , DeKosky Brandon J. TITLE=Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.615102 DOI=10.3389/fimmu.2021.615102 ISSN=1664-3224 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.