학술논문
Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients
Document Type
article
Author
Ahmed S. Fahad; Morgan R. Timm; Bharat Madan; Katherine E. Burgomaster; Kimberly A. Dowd; Erica Normandin; Matías F. 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
Source
Frontiers in Immunology, Vol 12 (2021)
Subject
Language
English
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.