The novel coronavirus, SARS-CoV-2 that causes COVID-19 has resulted in the death of nearly 4 million people within the last 18 months. While preventive vaccination, and monoclonal antibody therapies have been rapidly developed and deployed, early in the pandemic the use of COVID-19 convalescent plasma (CCP) was a common means of passive immunization with a theoretical risk of antibody-dependent enhancement (ADE) of viral infection. Though vaccines elicit a strong and protective immune response and transfusion of CCP with high titers of neutralization activity are correlated with better clinical outcomes, the question of whether antibodies in CCP can enhance infection of SARS-CoV-2 has not been directly addressed. In this study, we analyzed for and observed passive transfer of neutralization activity with CCP transfusion. Furthermore, to specifically understand if antibodies against the spike protein (S) enhance infection, we measured the anti-S IgG, IgA, and IgM responses and adapted retroviral-pseudotypes to measure virus neutralization with target cells expressing the ACE2 virus receptor and the Fc alpha receptor (FcαR) or Fc gamma receptor IIA (FcγRIIA). Whereas neutralizing activity of CCP correlated best with higher titers of anti-S IgG antibodies, the neutralizing titer was not affected when Fc receptors were present on target cells. These observations support the absence of antibody-dependent enhancement of infection (ADE) by IgG and IgA isotypes found in CCP. The results presented, therefore, not only supports the therapeutic use of currently available antibody-based treatment, including the continuation of CCP transfusion strategies, but also the use of various vaccine platforms in a prophylactic approach.
【초록키워드】 COVID-19, Treatment, convalescent plasma, passive immunization, antibodies, SARS-CoV-2, IgG, viral infection, ACE2, Vaccine, vaccination, pandemic, therapy, antibody, Antibody-dependent enhancement, monoclonal antibody, Infection, Prophylactic, immunization, clinical outcomes, Spike protein, Novel coronavirus, Neutralizing activity, IgA, Virus neutralization, death, Alpha, receptor, vaccine platform, virus receptor, transfusion, ADE, anti-S IgG, Neutralizing titer, Fc receptors, CCP, target cells, target cell, passive transfer, Support, observation, IgM responses, isotype, protective immune response, transfer, therapeutic use, neutralization activity, IgM response, while, theoretical risk, approach, ENhance, Fc receptor, analyzed, question, absence, the spike protein, correlated, elicit, cause, expressing, not affected, addressed, 【제목키워드】 COVID-19, IgG, ENhance, IgA antibody,