Functional Antibodies in COVID-19 Convalescent Plasma
Functional Antibodies in COVID-19 Convalescent Plasma
Abstract In the absence of an effective vaccine or monoclonal therapeutic, transfer of convalescent plasma (CCP) was proposed early in the SARS-CoV-2 pandemic as an easily accessible therapy. However, despite the global excitement around this historically valuable therapeutic approach, results from CCP trials have been mixed and highly debated. Unlike other therapeutic interventions, CCP represents a heterogeneous drug. Each CCP unit is unique and collected from an individual recovered COVID-19 patient, making the interpretation of therapeutic benefit more complicated. While the prevailing view in the field would suggest that it is administration of neutralizing antibodies via CCP that centrally provides therapeutic benefit to newly infected COVID-19 patients, many hospitalized COVID-19 patients already possess neutralizing antibodies. Importantly, the therapeutic benefit of antibodies can extend far beyond their simple ability to bind and block infection, especially related to their ability to interact with the innate immune system. In our work we deeply profiled the SARS-CoV-2-specific Fc-response in CCP donors, along with the recipients prior to and after CCP transfer, revealing striking SARS-CoV-2 specific Fc-heterogeneity across CCP units and their recipients. However, CCP units possessed more functional antibodies than acute COVID-19 patients, that shaped the evolution of COVID-19 patient humoral profiles via distinct immunomodulatory effects that varied by pre-existing SARS-CoV-2 Spike (S)-specific IgG titers in the patients. Our analysis identified surprising influence of both S and Nucleocapsid (N) specific antibody functions not only in direct antiviral activity but also in anti-inflammatory effects. These findings offer insights for more comprehensive interpretation of correlates of immunity in ongoing large scale CCP trials and for the design of next generation therapeutic design.
Chandran Kartik、Loos Carolin、Yoon Hyunah、Wang Chuangqi、Rivera Johanna、Haslwanter Denise、Jangra Rohit K.、Dieterle M. Eugenia、Herman Jonathan D.、Pirofski Liise-anne、Lauffenburger Douglas、Bortz Robert H. III、Alter Galit、Julg Boris、Bar Katharine J.
Department of Microbiology and Immunology. Albert Einstein College of MedicineRagon Institute of MGH, MIT, and Harvard||Department of Biological Engineering, Massachusetts Institute of TechnologyDivision of Infectious Diseases, Department of Medicine. Albert Einstein College of Medicine and Montefiore Medical CenterDepartment of Biological Engineering, Massachusetts Institute of TechnologyDivision of Infectious Diseases, Department of Medicine. Albert Einstein College of Medicine and Montefiore Medical Center||Department of Microbiology and Immunology. Albert Einstein College of MedicineDepartment of Microbiology and Immunology. Albert Einstein College of MedicineDepartment of Microbiology and Immunology. Albert Einstein College of MedicineDepartment of Microbiology and Immunology. Albert Einstein College of MedicineRagon Institute of MGH, MIT, and Harvard||Division of Infectious Disease, Brigham and Women?ˉs HospitalDivision of Infectious Diseases, Department of Medicine. Albert Einstein College of Medicine and Montefiore Medical Center||Department of Microbiology and Immunology. Albert Einstein College of MedicineDepartment of Biological Engineering, Massachusetts Institute of TechnologyDepartment of Microbiology and Immunology. Albert Einstein College of MedicineRagon Institute of MGH, MIT, and HarvardRagon Institute of MGH, MIT, and HarvardDepartment of Medicine, University of Pennsylvania
医药卫生理论医学研究方法基础医学
COVID-19SARS-CoV-2Convalescent PlasmaFunctional AntibodiesFc Effector FunctionsSystems Serology
Chandran Kartik,Loos Carolin,Yoon Hyunah,Wang Chuangqi,Rivera Johanna,Haslwanter Denise,Jangra Rohit K.,Dieterle M. Eugenia,Herman Jonathan D.,Pirofski Liise-anne,Lauffenburger Douglas,Bortz Robert H. III,Alter Galit,Julg Boris,Bar Katharine J..Functional Antibodies in COVID-19 Convalescent Plasma[EB/OL].(2025-03-28)[2025-04-26].https://www.medrxiv.org/content/10.1101/2021.03.08.21253157.点此复制
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