Broad dengue neutralization in mosquitoes expressing an engineered antibody

Anna Buchman (1) , Stephanie Gamez (1) , Ming Li (1) , Igor Antoshechkin (2) , Hsing-Han Li (3, 4, 5) , Hsin-Wei Wang (4, 5) , Chun-Hong Chen (4, 5) , Melissa Klein (6, 7) , Jean-Bernard Duchemin (6, 7) , James Crowe (8) , Prasad Paradkar (6, 7) , Omar S Akbari (1, 9)

1 Section of Cell and Developmental Biology
2 BBE - Division of Biology and Biological Engineering [Pasadena, USA]
3 NTHU - National Tsing Hua University [Hsinchu]
4 National Mosquito-Borne Diseases Control Research Center [Taiwan]
5 NHRI-IV - National Institute of Infectious Diseases and Vaccinology [Taiwan]
6 CSIRO Health and Biosecurity [Australia]
7 ACDP - Australian Centre for Disease Preparedness - Australian Animal Health Laboratory [Australia]
8 Vanderbilt University Medical Center [Nashville]
9 TIGS - Tata Institute for Genetics and Society's [La Jolla]

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.

Mots clés: Mosquitoes; Blood; Antibodies; Larvae; Genetic engineering; Saliva; Plasmid construction; Dengue virus

Domaines: Parasitologie; Virologie; Santé; Zoologie des invertébrés

Anna Buchman, Stephanie Gamez, Ming Li, Igor Antoshechkin, Hsing-Han Li, et al.. Broad dengue neutralization in mosquitoes expressing an engineered antibody. PLoS Pathogens, 2020, 16 (1), pp.e1008103. ⟨10.1371/journal.ppat.1008103⟩. ⟨pasteur-02653696⟩