Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire

Summary: Eliciting broad and potent HIV-specific neutralizing antibody responses represents the holy grail of HIV vaccine efforts. Data from singly infected individuals with broad and potent plasma neutralizing activity targeting one epitope have guided our understanding of how these responses devel...

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Main Authors: Katherine L. Williams, Bingjie Wang, Dana Arenz, James A. Williams, Adam S. Dingens, Valerie Cortez, Cassandra A. Simonich, Stephanie Rainwater, Dara A. Lehman, Kelly K. Lee, Julie Overbaugh
Format: Article
Language:English
Published: Elsevier 2018-04-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124718304431
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author Katherine L. Williams
Bingjie Wang
Dana Arenz
James A. Williams
Adam S. Dingens
Valerie Cortez
Cassandra A. Simonich
Stephanie Rainwater
Dara A. Lehman
Kelly K. Lee
Julie Overbaugh
author_facet Katherine L. Williams
Bingjie Wang
Dana Arenz
James A. Williams
Adam S. Dingens
Valerie Cortez
Cassandra A. Simonich
Stephanie Rainwater
Dara A. Lehman
Kelly K. Lee
Julie Overbaugh
author_sort Katherine L. Williams
collection DOAJ
description Summary: Eliciting broad and potent HIV-specific neutralizing antibody responses represents the holy grail of HIV vaccine efforts. Data from singly infected individuals with broad and potent plasma neutralizing activity targeting one epitope have guided our understanding of how these responses develop. However, far less is known about responses developed by superinfected individuals who acquire two distinct HIV strains. Here, we isolated HIV-specific mAbs from a superinfected individual with a broad plasma response. In this superinfection case, neutralizing activity resulted from multiple distinct B cell lineages that arose in response to either the initial or the superinfecting virus, including an antibody that targets the N332 supersite. This nAb, QA013.2, was specific to the superinfecting virus and was associated with eventual reemergence of the initial infecting virus. The complex dynamic between viruses in superinfection may drive development of a unique collection of polyclonal nAbs that present a higher barrier to escape than monoclonal responses. : Superinfection occurs when an HIV-infected person acquires a second infection with a genetically distinct HIV virus. Williams et al. isolate HIV-specific mAbs from a superinfected individual with a broad plasma response. In this superinfection case, neutralizing activity resulted from multiple distinct B cell lineages that arose in response to the initial or superinfecting virus, including an antibody that targets the N332 supersite. Keywords: HIV, antibody, broadly neutralizing antibody, HIV viral escape
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spelling doaj.art-d2f932fc2bb3434597cf2cf86c15ef2e2022-12-21T18:49:32ZengElsevierCell Reports2211-12472018-04-01233682691Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal RepertoireKatherine L. Williams0Bingjie Wang1Dana Arenz2James A. Williams3Adam S. Dingens4Valerie Cortez5Cassandra A. Simonich6Stephanie Rainwater7Dara A. Lehman8Kelly K. Lee9Julie Overbaugh10Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USADepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USADepartment of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USADivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Corresponding authorSummary: Eliciting broad and potent HIV-specific neutralizing antibody responses represents the holy grail of HIV vaccine efforts. Data from singly infected individuals with broad and potent plasma neutralizing activity targeting one epitope have guided our understanding of how these responses develop. However, far less is known about responses developed by superinfected individuals who acquire two distinct HIV strains. Here, we isolated HIV-specific mAbs from a superinfected individual with a broad plasma response. In this superinfection case, neutralizing activity resulted from multiple distinct B cell lineages that arose in response to either the initial or the superinfecting virus, including an antibody that targets the N332 supersite. This nAb, QA013.2, was specific to the superinfecting virus and was associated with eventual reemergence of the initial infecting virus. The complex dynamic between viruses in superinfection may drive development of a unique collection of polyclonal nAbs that present a higher barrier to escape than monoclonal responses. : Superinfection occurs when an HIV-infected person acquires a second infection with a genetically distinct HIV virus. Williams et al. isolate HIV-specific mAbs from a superinfected individual with a broad plasma response. In this superinfection case, neutralizing activity resulted from multiple distinct B cell lineages that arose in response to the initial or superinfecting virus, including an antibody that targets the N332 supersite. Keywords: HIV, antibody, broadly neutralizing antibody, HIV viral escapehttp://www.sciencedirect.com/science/article/pii/S2211124718304431
spellingShingle Katherine L. Williams
Bingjie Wang
Dana Arenz
James A. Williams
Adam S. Dingens
Valerie Cortez
Cassandra A. Simonich
Stephanie Rainwater
Dara A. Lehman
Kelly K. Lee
Julie Overbaugh
Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire
Cell Reports
title Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire
title_full Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire
title_fullStr Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire
title_full_unstemmed Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire
title_short Superinfection Drives HIV Neutralizing Antibody Responses from Several B Cell Lineages that Contribute to a Polyclonal Repertoire
title_sort superinfection drives hiv neutralizing antibody responses from several b cell lineages that contribute to a polyclonal repertoire
url http://www.sciencedirect.com/science/article/pii/S2211124718304431
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