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Background: Aedes aegypti presence, human-vector contact rates, and Aedes-borne virus transmission are highly variable through time and space. The Lower Rio Grande Valley (LRGV), Texas, is one of the few regions in the U.S. where local transmission of Aedes-borne viruses occurs, presenting an opportunity to evaluate social, urbanistic, entomological, and mobility-based factors that modulate human exposure to Ae. aegypti. Methodology & Principal findings: Mosquitoes were collected using BG-Sentinel 2 traps during November 2021 as part of an intervention trial, with knowledge, attitudes, and practices (KAP) and housing quality surveys to gather environmental and demographic data. Human blood samples were taken from individuals and a Bitemark Assay (ELISA) was conducted to quantify human antibodies to the Ae. aegypti Nterm-34kDa salivary peptide as a measure of human exposure to bites. In total, 64 houses were surveyed with 142 blood samples collected. More than 80% of participants had knowledge of mosquito-borne diseases and believed mosquitoes to be a health risk in their community. Our best fit generalized linear mixed effects model found four fixed effects contributed significantly to explaining the variation in exposure to Ae. aegypti bites: higher annual household income, younger age, larger lot area, and higher female Ae. aegypti abundance per trap night averaged over 5 weeks prior to human blood sampling. Conclusions: Most surveyed residents recognized mosquitoes and the threat they pose to individual and public health. Urbanistic (i.e., lot size), social (i.e., income within a low-income community and age), and entomological (i.e., adult female Ae. aegypti abundance) factors modulate the risk of human exposure to Ae. aegypti bites. The use of serological biomarker assays, such as the Bitemark Assay, are valuable tools for surveillance and risk assessment of mosquito-borne disease, especially in areas like the LRGV where the transmission of target pathogens is low or intermittent. Author summary: Aedes aegypti is a mosquito vector with public health importance on the global scale as it transmits viruses such as dengue, chikungunya, and Zika. Although transmission rates of dengue and Zika are low in the U.S., there are a few regions, including south Texas, where local transmission has occurred. Our study aimed to evaluate the factors associated with risk of exposure to these viruses using a serological bioassay that measured antibody response to an Ae. aegypti salivary protein to assess human-vector contact. We collected mosquitoes, took human-blood samples, and conducted urbanistic and demographic surveys in November 2021 in eight communities in the Lower Rio Grande Valley, Texas. Our knowledge, attitude, and practices survey found that most residents recognized adult mosquitoes, though few individuals knew someone personally who been sick with a mosquito-borne disease. Outdoor adult female Ae. aegypti abundance was positively associated with exposure to mosquito bites. Household income, individual age, and lot area also significantly affected exposure levels. The Bitemark Assay we used in this study can be utilized as a tool for entomological risk assessment and could be used as an alternative to infection exposure in areas where mosquito-borne disease levels are low. [ABSTRACT FROM AUTHOR]