The Animal Models Core, will serve three major purposes within the SARS Coronavirus Vaccine Development Program. 1) The core will develop standardized assays and reagents for evaluating the immune responses induced by wild-type SARS-CoV, as well as the panel of live attenuated, inactivated, and replicon vector delivered SARS-CoV vaccine candidates developed in projects 1-4 and Core C. 2) The core will evaluate the recombinant mutant SARS-CoV developed in this program project for effects on in vivo replication in a recently developed mouse model, and in vivo replication and pathogenesis in a ferret model of SARS-CoV-induced disease. These studies will provide important insights in to the role of specific viral genes in the pathogenesis of SARS-CoV respiratory infection. It is also expected that studies within this core will identify attenuated SARS-CoV mutants that whose safety profiles in the ferret will make them good candidates as live attenuated vaccines. 3) The core will perform a head to head comparison of live attenuated SARS-CoV vaccines that prove safe in the ferret model, as well as inactivated and replicon delivered vaccines. These studies will involve an in depth and stepwise assessment of each vaccine's ability to safely induce SARS-CoV specific immune responses and to protect from SARS-CoV challenge in the mouse and ferret models. The ultimate goal of this core, as well as the program project as a whole, is to develop candidate live attenuated, inactivated, or vector delivered vaccines that will safely and effectively protect against SARS-CoV infection. Vaccines that safely induce protective immunity against SARS-CoV challenge in the mouse and ferret models, will be considered to be good candidates for additional safety and efficacy testing in non-human primates. Specific Aims: Aim 1. Immune response assay development and optimization Aim 2. Evaluation of recombinant SARS-CoV for replication and disease phenotypes in small animal models. Aim 3. Evaluation of live attenuated, inactivated, VLP, and recombinant vector-based SARS-CoV vaccines for induction of protective immune responses.