Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients
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 a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.615102/full |
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| 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 Brandon J. DeKosky |
| author_facet | 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 Brandon J. DeKosky |
| author_sort | Ahmed S. Fahad |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T10:30:38Z |
| format | Article |
| id | doaj.art-f95e6840712f42789ca64171182a652b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T10:30:38Z |
| publishDate | 2021-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f95e6840712f42789ca64171182a652b2022-12-21T23:06:10ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011210.3389/fimmu.2021.615102615102Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease PatientsAhmed S. Fahad0Morgan R. Timm1Bharat Madan2Katherine E. Burgomaster3Kimberly A. Dowd4Erica Normandin5Matías F. Gutiérrez-González6Joseph M. Pennington7Matheus Oliveira De Souza8Amy R. Henry9Farida Laboune10Lingshu Wang11David R. Ambrozak12Ingelise J. Gordon13Daniel C. Douek14Julie E. Ledgerwood15Barney S. Graham16Leda R. Castilho17Theodore C. Pierson18John R. Mascola19Brandon J. DeKosky20Brandon J. DeKosky21Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesDepartment of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United StatesViral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesViral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesDepartment of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United StatesDepartment of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United StatesDepartment of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesFederal University of Rio de Janeiro, COPPE, Cell Culture Engineering Laboratory, Rio de Janeiro, BrazilViral Pathogenesis Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, United StatesDepartment of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS, United StatesDepartment of Chemical Engineering, The University of Kansas, Lawrence, KS, United StatesThe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.615102/fullZika virus (ZIKV)antiviral antibodiesB cellsyeast displaynext-generation sequencing |
| spellingShingle | 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 Brandon J. DeKosky Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients Frontiers in Immunology Zika virus (ZIKV) antiviral antibodies B cells yeast display next-generation sequencing |
| title | Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients |
| title_full | Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients |
| title_fullStr | Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients |
| title_full_unstemmed | Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients |
| title_short | Functional Profiling of Antibody Immune Repertoires in Convalescent Zika Virus Disease Patients |
| title_sort | functional profiling of antibody immune repertoires in convalescent zika virus disease patients |
| topic | Zika virus (ZIKV) antiviral antibodies B cells yeast display next-generation sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.615102/full |
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