Antibody-dependent enhancement (ADE) is a phenomenon by which non-neutralizing or sub-neutralizing antibodies bind to the virus and are then internalized by cells surface Fc Receptor, increasing virus entry. During the neutralizing process between SARS-CoV-2 and its antibody, the antibody Fab region will bind with receptor binding domain (RBD) on virus surface spike protein, blocking the virus entry. However, in ADE settings, the antibody Fc region interacts with cell surface Fc receptor, which leads to the entry of virus-antibody complex and causes ADE (Figure. 1).
Figure 1: ADE activity generation. Adapted from: Wu, F., Yan, R., Liu, M., Liu, Z., Wang, Y., Luan, D., ... & Huang, J. (2020). Antibody-dependent enhancement (ADE) of SARS-CoV-2 infection in recovered COVID-19 patients: Studies based on cellular and structural biology analysis. medRxiv.
ADE plays an essential role in SARS-CoV-2 vaccine and antibody drug development. ADE has exhibited dependency on antibody concentration and its neutralization ability, which are important aspects involved in vaccine design. Moreover, high ADE activity tightly correlates with high risks of lung injury in COVID-19 settings, which can result in failed vaccine development. In immunized macaques, a modified vaccinia Ankara viral vector expressing the SARS-CoV S protein had elicited anti-S IgG response which enhanced pulmonary infiltration of inflammatory macrophages and resulted in more severe lung injury compared to unvaccinated animals. Another experiment also confirmed that peptide vaccines induced antibodies can enhance infection in vitro and resulted in severe lung pathology in vivo. Regarding its impact on antibody responses and high risks in lung injury, ADE assay is an irreplaceable part of SARS-CoV-2 vaccine investigation.
Example Schematic of the ADE assay based on Pseudotyped Luciferase rSARS-CoV-2 Spike (CD Cat # COV-PS01)
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We provide a full serial of SARS-CoV-2 and SARS-CoV-2 Mutation pseudovirus with GFP or luciferase reporter gene as well as cell lines carrying the Fc Receptor or ACE2. See below Related Products for more information.