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Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

33 Pages Posted: 4 Jun 2019 Sneak Peek Status: Review Complete

See all articles by Anna Buchman

Anna Buchman

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

Stephanie Gamez

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

Ming Li

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

Igor Antoshechkin

California Institute of Technology - Division of Biology and Biological Engineering

Shin-Hang Lee

National Tsing Hua University

Shin-Wei Wang

National Health Research Institutes - National Institute of Infectious Diseases and Vaccinology

Chun-Hong Chen

National Health Research Institutes - National Institute of Infectious Diseases and Vaccinology

Melissa J. Klein

Australian Animal Health Laboratory

Jean-Bernard Duchemin

Australian Animal Health Laboratory

James E. Crowe

Vanderbilt University - Medical Center

Prasad N. Paradkar

Australian Animal Health Laboratory

Omar Akbari

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

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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.

Keywords: Dengue, Mosquito, Antibody

Suggested Citation

Buchman, Anna and Gamez, Stephanie and Li, Ming and Antoshechkin, Igor and Lee, Shin-Hang and Wang, Shin-Wei and Chen, Chun-Hong and Klein, Melissa J. and Duchemin, Jean-Bernard and Crowe, James E. and Paradkar, Prasad N. and Akbari, Omar, Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody (June 4, 2019). CELL-D-19-01515. Available at SSRN: https://ssrn.com/abstract=3398490 or http://dx.doi.org/10.2139/ssrn.3398490
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Anna Buchman

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

9500 Gilman Drive #108
La Jolla, CA 92093-0108
United States

Stephanie Gamez

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

9500 Gilman Drive #108
La Jolla, CA 92093-0108
United States

Ming Li

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology

9500 Gilman Drive #108
La Jolla, CA 92093-0108
United States

Igor Antoshechkin

California Institute of Technology - Division of Biology and Biological Engineering

Pasadena, CA 91125
United States

Shin-Hang Lee

National Tsing Hua University

Hsin Chu 3
China

Shin-Wei Wang

National Health Research Institutes - National Institute of Infectious Diseases and Vaccinology

35 Keyan Road
Zhunan, Miaoli County 350
Taiwan

Chun-Hong Chen

National Health Research Institutes - National Institute of Infectious Diseases and Vaccinology

35 Keyan Road
Zhunan, Miaoli County 350
Taiwan

Melissa J. Klein

Australian Animal Health Laboratory

Australia

Jean-Bernard Duchemin

Australian Animal Health Laboratory

Australia

James E. Crowe

Vanderbilt University - Medical Center

1211 Medical Center Dr
Nashville, TN 37232
United States

Prasad N. Paradkar

Australian Animal Health Laboratory

Australia

Omar Akbari (Contact Author)

University of California, San Diego (UCSD) - Section of Cell and Developmental Biology ( email )

9500 Gilman Drive #108
La Jolla, CA 92093-0108
United States

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