Coronavirus Challenge Core

Project Summary – Animal Challenge Core B The Animal Challenge Core B will develop and provide key virus stocks for four different human and animal coronaviruses (CoVs) that have pandemic potential. These viruses belong to the subgenera of Sarbecovirus and Merbecovirus and will be used by the Core for challenge studies

in mice and Syrian hamsters to evaluate cross-protective efficacy of vaccines against diverse betacoronaviruses. The virus stocks, generated by Core B, also will be used in virus neutralization assays prior to challenge or after immunogenicity testing of vaccines in mice and hamsters. The specific functions of Core B will include: (a) generating validated stocks of four different

betacoronaviruses including SARS-CoV-1, SARS-CoV-2, SHC-014 and pangolin/MP789/2019; (b) developing rodent models for bat coronaviruses; (c) Contributing to and performing pivotal immunogenicity studies in mice and hamsters to quantify the B and T cell response to vaccination with different vaccine candidates generated in Projects 1-3; (d) Performing virus challenge

studies with human and bat CoV in mice and hamsters immunized with candidate vaccines that induce broadly reactive B- and T-cell responses to diverse betacoronaviruses. The results from Core B will be used by the data management team in Core A to identify correlates of immune cross-protection against betacoronaviruses of pandemic concern. These functons will enable the

PPG group to determine whether a candidate vaccine induces broadly protective immunity against human and animal CoV. This Core B, led by Drs. Frieman and Boon, will meet the needs of the PPG by acquiring and generating challenge viruses, developing animal models and performing immunogenicity and vaccine challenges studies in established rodent models of

betacoronaviruses. These functions provide key infrastructure support for all research projects of the PPG.