Large-scale Analysis of CoVIC Antibodies by a Global Consortium Identifies Predictors of in Vivoprotection

Abstract The Coronavirus Immunotherapeutic Consortium (CoVIC) was established to develop prevention and therapeutic strategies against SARS-CoV-2 that could be used in low- and middle-income countries. The CoVIC compiled a unique panel comprising nearly 400 candidate therapeutic antibodies contributed by 60 groups in industry, academic, and government settings. All antibodies in the CoVIC panel were first blinded at the CoVIC headquarters at the La Jolla Institute for Immunology through the assignment of a code name. Identical sets of antibodies were then sent under the assigned code names to seven different partner reference labs that carried out side-by-side, standardized analyses of binding affinity, epitope location, high resolution structures, pseudovirus and authentic virus neutralization, in vivo protection, and Fc-mediated effector functions. The reference labs deposited their data, which was then validated and made publicly accessible, in the CoVIC database (CoVIC-DB). Using various statistical analyses of the data, we investigated relationships among functional properties of the antibodies. For example, we could discern that binding affinity to the full-length spike is more predictive of neutralization potency than binding affinity to the RBD, and that binding affinity and epitope location together correlates with neutralization. However, neutralization alone is not sufficient to explain in vivo protection in the K18 mouse model of SARS-CoV-2 infection, as other factors such as antibody pharmacokinetics were also important. Overall, the results of this study revealed important insights into antibody properties that are good predictors of in vivo protection by CoVIC antibodies. COVIC-19 Therapeutics Accelerator (a partnership of Bill and Melinda Gates Foundation), Bill and Melinda Gates Foundation, Mastercard, Wellcome Trust, National Institute of Allergy and Infectious Diseases of the National Institutes of Health, GHR Foundation, FastGrant from Emergent Ventures