Broad dengue neutralization in mosquitoes expressing an engineered antibody


Autoři: Anna Buchman aff001;  Stephanie Gamez aff001;  Ming Li aff001;  Igor Antoshechkin aff002;  Hsing-Han Li aff003;  Hsin-Wei Wang aff004;  Chun-Hong Chen aff004;  Melissa J. Klein aff006;  Jean-Bernard Duchemin aff006;  James E. Crowe, Jr. aff007;  Prasad N. Paradkar aff006;  Omar S. Akbari aff001
Působiště autorů: Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, California, United States of America aff001;  Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, United States of America aff002;  Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan aff003;  National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan aff004;  National Mosquito-Borne Diseases Control Research Center, National Health Research Institutes, Zhunan, Taiwan aff005;  CSIRO Health and Biosecurity, Australian Animal Health Laboratory, Geelong, VIC, Australia aff006;  Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff007;  Departments of Pediatrics, Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff008;  Tata Institute for Genetics and Society-UCSD, La Jolla, California, United States of America aff009
Vyšlo v časopise: Broad dengue neutralization in mosquitoes expressing an engineered antibody. PLoS Pathog 16(1): e1008103. doi:10.1371/journal.ppat.1008103
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008103

Souhrn

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.

Klíčová slova:

Antibodies – Blood – Dengue virus – Genetic engineering – Larvae – Mosquitoes – Plasmid construction – Saliva


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