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

Autor:	Williams KL; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA., Wang B; Division 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, USA., Arenz D; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA., Williams JA; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Dingens AS; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA., Cortez V; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA; Program in Molecular and Cellular Biology, University of Washington, Seattle, WA 98195, USA., Simonich CA; Division 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, USA., Rainwater S; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA., Lehman DA; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA., Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA., Overbaugh J; Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98195, USA. Electronic address: joverbau@fhcrc.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Apr 17; Vol. 23 (3), pp. 682-691.
DOI:	10.1016/j.celrep.2018.03.082
Abstrakt:	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. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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