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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 Lee, Shin-Hang 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. (2019) Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody. . (Unpublished) http://resolver.caltech.edu/CaltechAUTHORS:20190524-084310756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:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/645481DOIArticle
https://www.biorxiv.org/content/10.1101/645481v1OrganizationDiscussion Paper
ORCID:
AuthorORCID
Buchman, Anna0000-0002-8775-6147
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:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. bioRxiv preprint first posted online May. 24, 2019. Author Contributions: A.B., P.N.P., C.H.C., and O.S.A. conceived and designed the experiments. A.B., S.G., M.L., SH. L., and S-W.W. performed all molecular and genetic experiments. I.A. performed sequencing and bioinformatic analysis. J.E.C. provided sequence data for the 1C19 monoclonal antibody. M.J.K., J.B.D., and P.N.P. performed and analyzed all data for DENV mosquito challenge assays. All authors contributed to the writing and approved the final manuscript. 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. We thank Prof. Scott O’Neill (Institute of Vector Borne Diseases, Monash University, Australia) and the World Mosquito Program for providing Wolbachia-infected mosquito eggs. Data Availability Statement: All sequencing data associated with this study are available from the NCBI sequence read archive (SRA) accession ID: PRJNA510258. The complete annotated plasmid sequence and DNA is publicly available at Addgene (plasmid #120362 [OA984-HA] and #120363 [OA984]). Transgenic mosquitoes will be made available by the corresponding authors upon request. Competing interests: 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.
Funders:
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0047
NIH1R21AI123937
Commonwealth Scientific and Industrial Research Organisation (CSIRO)UNSPECIFIED
Record Number:CaltechAUTHORS:20190524-084310756
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20190524-084310756
Official Citation:Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody. Anna Buchman, Stephanie Gamez, Ming Li, Igor Antoshechkin, Shin-Hang Lee, Shin-Wei Wang, Chun-Hong Chen, Melissa J Klein, Jean-Bernard Duchemin, James E Crowe Jr., Prasad N Paradkar, Omar Akbari. bioRxiv 645481; doi: https://doi.org/10.1101/645481
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:24 May 2019 16:16

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