Broad dengue neutralization in mosquitoes expressing an engineered antibody.

With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with...

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Main Authors: Anna Buchman, Stephanie Gamez, Ming Li, Igor Antoshechkin, Hsing-Han Li, Hsin-Wei Wang, Chun-Hong Chen, Melissa J Klein, Jean-Bernard Duchemin, James E Crowe, Prasad N Paradkar, Omar S Akbari
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1008103
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author Anna Buchman
Stephanie Gamez
Ming Li
Igor Antoshechkin
Hsing-Han Li
Hsin-Wei Wang
Chun-Hong Chen
Melissa J Klein
Jean-Bernard Duchemin
James E Crowe
Prasad N Paradkar
Omar S Akbari
author_facet Anna Buchman
Stephanie Gamez
Ming Li
Igor Antoshechkin
Hsing-Han Li
Hsin-Wei Wang
Chun-Hong Chen
Melissa J Klein
Jean-Bernard Duchemin
James E Crowe
Prasad N Paradkar
Omar S Akbari
author_sort Anna Buchman
collection DOAJ
description With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.
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spelling doaj.art-eb7f58b3071e483784b8e478e7845c302022-12-21T19:55:40ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-01-01161e100810310.1371/journal.ppat.1008103Broad dengue neutralization in mosquitoes expressing an engineered antibody.Anna BuchmanStephanie GamezMing LiIgor AntoshechkinHsing-Han LiHsin-Wei WangChun-Hong ChenMelissa J KleinJean-Bernard DucheminJames E CrowePrasad N ParadkarOmar S AkbariWith dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses.https://doi.org/10.1371/journal.ppat.1008103
spellingShingle Anna Buchman
Stephanie Gamez
Ming Li
Igor Antoshechkin
Hsing-Han Li
Hsin-Wei Wang
Chun-Hong Chen
Melissa J Klein
Jean-Bernard Duchemin
James E Crowe
Prasad N Paradkar
Omar S Akbari
Broad dengue neutralization in mosquitoes expressing an engineered antibody.
PLoS Pathogens
title Broad dengue neutralization in mosquitoes expressing an engineered antibody.
title_full Broad dengue neutralization in mosquitoes expressing an engineered antibody.
title_fullStr Broad dengue neutralization in mosquitoes expressing an engineered antibody.
title_full_unstemmed Broad dengue neutralization in mosquitoes expressing an engineered antibody.
title_short Broad dengue neutralization in mosquitoes expressing an engineered antibody.
title_sort broad dengue neutralization in mosquitoes expressing an engineered antibody
url https://doi.org/10.1371/journal.ppat.1008103
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