Contribution of antibody-dependent enhancement to the pathogenesis of coronavirus infections

Since the emergence of the SARS-CoV-2 virus in late 2019, vaccines against the COVID-19 infection have been under development using different approaches. At present, protective immunity factors against COVID-19 infection are not completely characterized. Of the four structural proteins of coronavirus, the spike protein (S) and the nucleocapsid protein (N) are most widely expressed in viral infections and elicit the antibody response. Antibody-dependent enhancement (ADE) presents a problem for developing a vaccine against SARS-CoV. It was shown in animal studies that SARS-CoV-1 vaccines containing recombinant S-protein or DNA-vaccine expressed S-protein led to pulmonary immunopathology after infection with SARS virus. Antibodies to the coronavirus S-protein produced by the human immune system in response to infection may contribute to the penetration of SARS-CoV into monocytes and macrophages through the Fc-gamma receptor (Fc gamma R) and may aggravate the course of infection. The demonstration of ADE with coronavirus infection raises fundamental questions regarding the development of vaccines against the SARS-CoV-2 virus and the use of passive prophylaxis or treatment with virus-specific monoclonal antibodies. Evaluation of the mechanisms of immunopathology, including the responses of immunoglobulins and cytokines to vaccines, and tests for antigen-antibody complexes after infection and vaccination can help address these issues.