Sự thoát khỏi kháng thể trung hoà của các biến thể protein gai SARS-CoV-2

eLife - Tập 9
Yiska Weisblum1, Fabian Schmidt1, Fengwen Zhang1, Justin DaSilva1, Daniel Poston1, Julio C. C. Lorenzi2, Frauke Muecksch1, Magdalena Rutkowska1, Hans-Heinrich Hoffmann3, Eleftherios Michailidis3, Christian Gaebler2, Marianna Agudelo2, Alice Cho2, Zijun Wang2, Anna Gazumyan2, Melissa Cipolla2, Larry L. Luchsinger4, Christopher D. Hillyer4, Marina Caskey2, Davide F. Robbiani5,2, Charles M. Rice3, Michel C. Nussenzweig6,2, Théodora Hatziioannou1, Paul D. Bieniasz6,1
1Laboratory of Retrovirology, The Rockefeller University, New York, United States
2Laboratory of Molecular Immunology The Rockefeller University, New York, United States
3Laboratory of Virology and Infectious Disease The Rockefeller University, New York, United States
4Lindsley F. Kimball Research Institute, New York Blood Center, New York, United States
5Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
6Howard Hughes Medical Institute, The Rockefeller University, New York, United States

Tóm tắt

Kháng thể trung hoà được tạo ra bởi nhiễm trùng trước đó hoặc tiêm chủng có khả năng đóng vai trò quan trọng trong việc bảo vệ tương lai cho cá nhân và quần thể chống lại SARS-CoV-2. Hơn nữa, các kháng thể được tiêm chủng một cách thụ động nằm trong số những tác nhân điều trị và dự phòng chống SARS-CoV-2 khả thi nhất. Tuy nhiên, mức độ mà SARS-CoV-2 sẽ thích nghi để né tránh các kháng thể trung hoà vẫn chưa rõ ràng. Sử dụng virus báo cáo VSV/SARS-CoV-2 tái tổ hợp, chúng tôi cho thấy rằng các biến thể protein S của SARS-CoV-2 chức năng có đột biến trong miền liên kết thụ thể (RBD) và miền đầu N mà mang lại khả năng kháng lại các kháng thể đơn dòng hoặc huyết tương hồi phục có thể dễ dàng được chọn lọc. Đáng chú ý, các biến thể S của SARS-CoV-2 kháng lại các kháng thể trung hoà thường được tạo ra hiện đang xuất hiện với tần suất thấp trong các quần thể SARS-CoV-2 lưu hành. Cuối cùng, sự xuất hiện của các biến thể SARS-CoV-2 kháng kháng thể mà có thể hạn chế tính hữu ích điều trị của các kháng thể đơn dòng có thể được giảm thiểu bằng cách sử dụng các tổ hợp kháng thể nhằm vào các epitope trung hoà khác nhau.

Từ khóa


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