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Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

Buchman, Anna and Gamez, Stephanie and Li, Ming and Antoshechkin, Igor and Li, Hsing-Han and Wang, Shin-Wei and Chen, Chun-Hong and Klein, Melissa J. and Duchemin, Jean-Bernard and Crowe, James E., Jr. and Paradkar, Prasad N. and Akbari, Omar S. (2020) Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody. PLoS Pathogens, 16 (1). Art. No. e1008103. ISSN 1553-7366. PMCID PMC6964813. https://resolver.caltech.edu/CaltechAUTHORS:20190524-084310756

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Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1371/journal.ppat.1008103DOIArticle
https://doi.org/10.1101/645481DOIDiscussion Paper
https://doi.org/10.1371/journal.ppat.1008103.s001DOIS1 Fig.
https://doi.org/10.1371/journal.ppat.1008103.s002DOIS2 Fig.
https://doi.org/10.1371/journal.ppat.1008103.s003DOIS3 Fig.
https://doi.org/10.1371/journal.ppat.1008103.s004DOIS4 Fig.
https://doi.org/10.1371/journal.ppat.1008103.s005DOIS1 Table
https://doi.org/10.1371/journal.ppat.1008103.s006DOIS2 Table
https://doi.org/10.1371/journal.ppat.1008103.s007DOIS3 Table
https://doi.org/10.1371/journal.ppat.1008103.s008DOIS4 Table
https://doi.org/10.1371/journal.ppat.1008103.s009DOIS5 Table
https://doi.org/10.1371/journal.ppat.1008103.s010DOIS6 Table
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964813/PubMed CentralArticle
ORCID:
AuthorORCID
Buchman, Anna0000-0002-8775-6147
Gamez, Stephanie0000-0003-0665-0066
Antoshechkin, Igor0000-0002-9934-3040
Duchemin, Jean-Bernard0000-0001-5044-4855
Crowe, James E., Jr.0000-0002-0049-1079
Akbari, Omar S.0000-0002-6853-9884
Additional Information:© 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. Received: July 18, 2019; Accepted: September 23, 2019; Published: January 16, 2020. Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.ppat.1008103 Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. This 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 manuscript. Competing interests: O.S.A is a founder and serves on the scientific advisory board for Agragene. J.E.C. has served as a consultant for Takeda Vaccines, Sanofi Pasteur, Pfizer, and Novavax, is on the Scientific Advisory Boards of CompuVax, GigaGen, Meissa Vaccines, and is the Founder of IDBiologics, Inc. All other authors declare no competing financial interests. Author Contributions: Conceptualization: Prasad N. Paradkar, Omar S. Akbari. Data curation: Anna Buchman, Stephanie Gamez, Ming Li, Igor Antoshechkin, Hsing-Han Li, Hsin-Wei Wang, Melissa J. Klein, Jean-Bernard Duchemin, Prasad N. Paradkar. Formal analysis: Anna Buchman, Igor Antoshechkin, Hsin-Wei Wang, Chun-Hong Chen, Melissa J. Klein. Funding acquisition: Omar S. Akbari. Investigation: Stephanie Gamez, Ming Li, Hsing-Han Li, Hsin-Wei Wang, Chun-Hong Chen, Melissa J. Klein, James E. Crowe, Jr., Prasad N. Paradkar. Methodology: James E. Crowe, Jr., Prasad N. Paradkar. Resources: James E. Crowe, Jr., Prasad N. Paradkar. Writing – original draft: Anna Buchman, Igor Antoshechkin, Prasad N. Paradkar, Omar S. Akbari. Writing – review & editing: Anna Buchman, Stephanie Gamez, Igor Antoshechkin, Chun-Hong Chen, Prasad N. Paradkar, Omar S. Akbari.
Funders:
Funding AgencyGrant Number
Defense Advanced Research Project Agency (DARPA)HR0011-17-2-0047
NIH1R21AI123937
Commonwealth Scientific and Industrial Research Organisation (CSIRO)UNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC6964813
Record Number:CaltechAUTHORS:20190524-084310756
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190524-084310756
Official Citation:Buchman 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. https://doi.org/10.1371/journal.ppat.1008103
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95776
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 May 2019 16:16
Last Modified:10 Feb 2020 21:08

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