Location: Foreign Arthropod Borne Animal Disease Research
Project Number: 3022-32000-025-035-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Sep 1, 2026
End Date: Aug 31, 2029
Objective:
The objective of this NACA is to develop a porcine hydrogel-based skin system that can be used to examine virus-vector-host interactions. The hydrogel skin system mimics a vascularized skin model and allows for detailed in vitro study of cells infected by natural mosquito bites; thereby, allowing for direct measurement of arboviral uptake and transmission events.
Approach:
The biocompatibility of the hydrogels allows for culturing of living cells on and/or within the gel matrix. The hydrogel skin system (HSS) allows for the embedding and culture of living cells and is highly flexible and adaptable to different cell types. With the commercial availability of porcine dermal cells (e.g. fibroblasts and keratinocytes), these studies will utilize this flexibility by embedding porcine dermal cells in the HSS. Virus-infected laboratory reared mosquitoes will be allowed to feed on the cellularized HSS. The ability of the hydrogel skin system to replicate in vivo virus-vector-host interactions (e.g., virus-saliva interactions) in a defined, cellularized in vitro system will be evaluated. This can be evaluated via several methods such as detection of salivary proteins, measure of immune responses, replication kinetics of the virus, or examining the anti-viral response of the host. In addition, the ability of HSS to supplant whole animal repellent testing will be examined using topical (e.g. Permethrin) and systemic (e.g. Ivermectin) agents. The effects of repellent can be measured, for example, by looking at virus replication in the system, the effects on the feeding behavior of the mosquitoes. Taken together, these data will demonstrate the potential of the HSS to replace animal models in arboviral infection experiments.