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Title: High-avidity and potently neutralizing cross-reactive human monoclonal antibodies derived from secondary dengue virus infection
Authors: Wen Yang Tsai
Chih Yun Lai
Yi Chieh Wu
Hong En Lin
Carolyn Edwards
Amonrat Jumnainsong
Srisakul Kliks
Scott Halstead
Juthathip Mongkolsapaya
Gavin R. Screaton
Wei Kung Wang
University of Hawaii at Manoa John A. Burns School of Medicine
National Taiwan University College of Medicine
International Vaccine Institute, Seoul
Imperial College London
Mahidol University
Khon Kaen University
Keywords: Immunology and Microbiology
Issue Date: 1-Dec-2013
Citation: Journal of Virology. Vol.87, No.23 (2013), 12562-12575
Abstract: The envelope (E) protein of dengue virus (DENV) is the major target of neutralizing antibodies (Abs) and vaccine development. Previous studies of human dengue-immune sera reported that a significant proportion of anti-E Abs, known as group-reactive (GR) Abs, were cross-reactive to all four DENV serotypes and to one or more other flaviviruses. Based on studies of mouse anti-E monoclonal antibodies (MAbs), GR MAbs were nonneutralizing or weakly neutralizing compared with type-specific MAbs; a GR response was thus not regarded as important for vaccine strategy. We investigated the epitopes, binding avidities, and neutralization potencies of 32 human GR anti-E MAbs. In addition to fusion loop (FL) residues in E protein domain II, human GR MAbs recognized an epitope involving both FL and bc loop residues in domain II. The neutralization potencies and binding avidities of GR MAbs derived from secondary DENV infection were stronger than those derived from primary infection. GR MAbs derived from primary DENV infection primarily blocked attachment, whereas those derived from secondary infection blocked DENV postattachment. Analysis of the repertoire of anti-E MAbs derived from patients with primary DENV infection revealed that the majority were GR, low-avidity, and weakly neutralizing MAbs, whereas those from secondary infection were primarily GR, high-avidity, and potently neutralizing MAbs. Our findings suggest that the weakly neutralizing GR anti-E Abs generated from primary DENV infection become potently neutralizing MAbs against the four serotypes after secondary infection. The observation that the dengue immune status of the host affects the quality of the cross-reactive Abs generated has implications for new strategies for DENV vaccination. © 2013, American Society for Microbiology.
ISSN: 10985514
Appears in Collections:Scopus 2011-2015

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