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Broad dengue neutralization in mosquitoes expressing an engineered antibody

dc.contributor.authorCrowe, James E., Jr.
dc.identifier.citationBuchman A, Gamez S, Li M, Antoshechkin I, Li H-H, Wang H-W, et al. (2020) Broad dengue neutralization in mosquitoes expressing an engineered antibody. PLoS Pathog 16(1): e1008103. ppat.1008103en_US
dc.descriptionOnly Vanderbilt University affiliated authors are listed on VUIR. For a full list of authors, access the version of record at
dc.description.abstractAuthor summary With limited success of traditional vector control methods to curb dengue infections and more than half of the world's population still at risk, there is a need for novel strategies to reduce its impact on public health. Recent advances in genetic technologies has allowed for precise modifications of mosquito genome to make them resistant to infections, thus breaking the transmission cycle. Here we generated engineered Ae. aegypti mosquitoes efficiently expressing a DENV-targeting single-chain variable fragment (scFv) derived from a previously characterized broadly neutralizing human antibody, which blocked infection and transmission in these mosquitoes. To our knowledge, this is the first example of an engineered transgene capable of rendering Ae. aegypti mosquitoes 100% refractory to all four serotypes of DENV. The engineered mosquitoes, in future, could easily be paired with a gene drive, capable of spreading the transgene throughout wild disease-transmitting mosquito populations and preventing further DENV transmission. Since a number of diverse and well-characterized antibodies exist against other arboviruses (eg chikungunya and Zika, this work also provides a proof-of-concept principle for developing similar genetic strategies for reducing the impact of these arboviruses. 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.en_US
dc.description.sponsorshipThis work was supported in part by a Defense Advanced Research Project Agency (DARPA) Safe Genes Program Grant (HR0011-17-2-0047) awarded to O.S.A. and a NIH Exploratory/Developmental Research Grant Award (1R21AI123937) awarded to O.S.A and CSIRO internal funding to P.N.P. The funders had no role in study design, data collection, analysis, the decision to publish, nor the preparation of the manuscripten_US
dc.publisherPLoS Pathogensen_US
dc.rightsCopyright: © 2020 Buchman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.titleBroad dengue neutralization in mosquitoes expressing an engineered antibodyen_US

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