Summary/Abstract Robust animal models of coronavirus infection are required for pre-clinical assessment of candidate vaccines and therapeutic antibodies to prevent coronavirus infection and disease. The goal of the Animal Model Core is to provide a central resource of animal models and virological tools to assess the effectiveness of vaccines and antibody therapies against betacoronaviruses in multiple animal models of infection. An experienced team of investigators will utilize established hamster, mouse, and ferret models of betacoronavirus infection to determine the efficacy of candidate therapeutic monoclonal antibodies (mAbs) developed by Project 1 and vaccines developed by Project 2. Pre-immune and transmission models will be utilized to stringently test the lead candidate vaccines. The Animal Model Core will also establish novel animal infection models with SARS- CoV-2 variant viruses, and a novel ferret model of OC43 embecovirus infection. The Animal Model Core will also complete virus neutralization assays for SARS-CoV and MERS CoV for all PLUTO investigators, centralizing resources for these viruses, eliminating redundant biosafety and Select Agent approvals. The Animal Model Core will serve as an innovative resource to assess efficacy of leading vaccine and mAb candidates for the PLUTO program through the following three Specific Aims. 1) Establish and maintain animal models of sarbecovirus and merbecovirus infection. 2) Establish and maintain coronavirus pre-immune animal models. 3) Expand and improve animal models of embecovirus and sarbecovirus infection. These complementary aims will enable rigorous assessment of vaccines and mAbs developed by the PLUTO Projects and develop new animal models of betacoronavirus infection for the project and respiratory virus research community. The novel pre-immune models will also provide data and samples to improve understanding of the impact of pre-existing betacoronavirus immunity on subsequent vaccination and infection. The outcomes of the Animal Model Core will have a positive impact on the success of the PLUTO program and provide novel information and research tools for the broader research community.