nAbs Derived from Animals
Animal models represent another tool to generate nAbs against SARS-CoV-2 (Table 3). In one study, the authors developed a protocol to synthetize human nanobodies, smaller antibodies that only contain a variable heavy (VH) chain as first described in camelids (Wu et al., 2020c) (Figure 6D). Another antibody isolated from camelids immunized with SARS-CoV-1 and MERS-CoV S proteins then fused to a human Fc fragment showed neutralization potential against SARS-CoV-2 (VHH-72-Fc) (Wrapp et al., 2020). Genetically modified mice with humanized antibody genes can also be used to generate therapeutic monoclonal antibodies, as successfully experimented against Ebola virus (Levine, 2019). Similar studies are now focused on the use of SARS-CoV-2 or derivatives to generate highly effective nAb in animal models, which can be directly given to infected patients, and efforts are already underway with estimates of clinical trials of pooled antibody cocktails beginning in early summer by Regeneron. Finally, another approach to nAb development is to fuse ACE2 protein and the Fc part of antibodies, as they would bind RBD and potentially be crossreactive among other CoVs (Figure 6D). Indeed, an ACE2-Fc (Lei et al., 2020a) and an RBD-Fc (Li et al., 2020d) have been shown to neutralize both SARS-CoV-1 and SARS-CoV-2 in vitro.