Safety and efficacy of SARS-CoV-2 antibodies

Treatment for COVID-19 is urgently needed but safety and efficacy of novel candidate therapeutics need to be assessed first before phase 1 clinical trials start. Therefore, appropriate in vitro and in vivo assays need to be included in a pre-clinical development workflow. These assays need to be carefully selected, optimized and streamlined in order to provide the appropriate data for rapid response and treatment development. The knowledge on COVID-19 intervention strategies and potential side effects of those is now accumulating, and a pre-clinical safety and efficacy assessment workflow needs to be able to easily and rapidly accommodate additional assays. One of the promising treatment options for COVID-19 includes the use of virus-neutralizing antibodies that block virus entry into the cell and thus are considered powerful means to block viral infection. However, several studies suggest that low level (non)-neutralizing antibodies may pose a risk for severe lung disease on virus re-exposure. The latter should be included in the safety assessment of candidate antibodies as early as possible in order to prioritize Abs that are not going to fail in the later stage of the (pre-) clinical development. The current proposed project aims at contributing to the rapid international public health response against SARS-CoV-2 by (i) testing the efficacy and safety of lead candidate SARS-CoV-2 neutralizing monoclonal antibodies (e.g. the antibody 49D11 and others identified by Erasmus MC and AMC) using in vitro assays and in vivo animal models; and by (ii) developing, validating and sharing with the research community a workflow of protocols for rapid testing of the efficacy and safety of recently identified candidate antiviral antibodies and plasma preparations for (a) efficacy and safety in in vitro systems; and (b) efficacy and safety in in vivo animal models. Altogether, we aim to bring a candidate Ab to a phase 1 clinical trial and to provide the research and development community with a streamlined workflow for the rapid efficacy and safety assessment of novel Ab-based therapeutics against COVID-19.