Characterization of Skin Immunity to Aedes Aegypti Saliva in Dengue-endemic Participants in Cambodia

Mosquito-borne viruses continue to cause significant global morbidity and mortality, particularly in Southeast Asia. When mosquitoes deliver the virus into the skin of humans while probing for a blood meal, they deposit also saliva, which contains a myriad of pharmacologically active compounds that modulate the host immune system. Little is known about skin immunity to mosquito saliva, particularly in endemic volunteers as most clinical studies are performed in na(SqrRoot) ve individuals who have never or rarely been exposed to a particular mosquito vector. People living in endemic areas have had long-term repeated exposure to these vectors and therefore have different immune response to mosquito saliva, which could interfere with mosquito-borne disease vaccine effectiveness. Characterization of skin immunity via various technical modalities will be important in order to identify critical aspects of the innate and adaptive immune responses after a vector bite.Here, we will execute a paired study of exposed-unexposed skin to carefully examine the innate and adaptive immune responses in the skin and blood to exposure of the saliva of Aedes aegypti, the mosquito vector of dengue, Zika, and chikungunya viruses. We will enroll 42 participants to undergo vector feeding and give blood samples at baseline and 2 and 14 days later. Additionally, participants will give skin punch biopsy samples of bitten (exposed) and unbitten (unexposed) skin. For analysis, we will group 10-12 participants in each of 4 technical modality cohorts or groups : 1) immunohistochemistry, 2) RNA sequencing, 3) flow cytometry, and 4) T-cell receptor sequencing. With the current rise of vector-borne diseases in the United States and around the world, we hope the results of this study contribute to future vaccine design and clinical development strategies for vector#borne diseases.