Delineating barriers to the effectiveness of wolbachia-based interventions for arboviral risk reduction

The National Institute of Allergy and Infectious Diseases awarded Yale University $100,228 on February 11, 2028, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to support research delineating barriers to the effectiveness of Wolbachia-based interventions for arboviral risk reduction.

The research, conducted entirely in the United States and performed in Connecticut, investigates mechanisms driving inconsistent Wolbachia establishment in Aedes aegypti mosquitoes to optimize these interventions before wider implementation in U.S. areas at risk for dengue and other Aedes-borne diseases. The project leverages longitudinal datasets and samples from Wolbachia release programs in three Brazilian cities, including the NIAID-sponsored EVITA dengue cluster randomized controlled trial, to examine two critical determinants of intervention success. The first aim delineates meteorological and environmental factors influencing partial and complete Wolbachia loss by integrating field measurements with molecular markers to develop statistical and mathematical models characterizing patterns and drivers of loss. The second aim uses whole-genome sequencing data to determine how fine-scale Aedes aegypti population structure influences Wolbachia introgression dynamics following releases.

The award period of performance runs from February 11, 2028, through August 15, 2028.

Abstract

Dengue and other aedes-borne diseases pose a significant and increasing public health challenge in southern U.S. States and territories, where aedes aegypti is established and local transmission has already occurred. At present, there is no effective prevention of aedes-borne diseases in the U.S. Wolbachia-based interventions are a novel strategy for reducing arboviral transmission by aedes aegypti, but their effectiveness has varied across settings. There is therefore an urgent need to identify the mechanisms driving inconsistent wolbachia establishment such that these interventions can be optimized before wider implementation in areas at risk in the U.S. We have a unique opportunity to interrogate these mechanisms in brazil, which is implementing large scale releases of wolbachia-infected mosquitoes. My preliminary work has shown marked spatial heterogeneity in wolbachia introgression across multiple brazilian cities following releases. This proposal, which will be conducted entirely in the U.S., leverages longitudinal datasets and samples from wolbachia release programs provided by our collaborators from three brazilian cities, including the niaid-sponsored evita dengue cluster randomized controlled trial, to investigate two critical determinants of intervention success. Specifically, this proposal aims to: (1) delineate the meteorological and environmental factors that influence partial and complete wolbachia loss in AE. Aegypti, and (2) determine how fine-scale AE. Aegypti population structure influences wolbachia introgression dynamics after releases. For the first aim, i will integrate field measurements of wolbachia introgression with molecular markers of wolbachia loss to develop statistical and mathematical models characterizing patterns and drivers of loss. For the second aim, i will use whole-genome sequencing data to quantify genetic differentiation, connectivity, and kinship structure in AE. Aegypti populations prior to releases in belo horizonte. I will then assess whether these features predict spatial patterns of introgression following deployments. The successful completion of the proposed project will inform models to guide site selection, optimize the design of release plans, pinpoint modifiable landscape features that can improve introgression, and set benchmarks for the development of more resilient wolbachia strains in the future, thus strengthening the evidence base necessary for scaling these interventions. Furthermore, by identifying environmental and genetic barriers to successful wolbachia establishment, this project will generate operational guidance directly relevant to protecting americans from dengue and other aedes-borne diseases in high-risk regions. Finally, the proposed mentoring from experts in the field, didactic training, and skill building activities will prepare a U.S. Physician-scientist in vector genomics, spatial epidemiology, and mathematical modeling and strengthen U.S. Scientific leadership in vector-borne disease research and preparedness.