Cell host & microbe · 2018
A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection against Ebola Virus.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gunn Bronwyn M, Yu Wen-Han, Karim Marcus M, Brannan Jennifer M, Herbert Andrew S, Wec Anna Z, Halfmann Peter J, Fusco Marnie L, Schendel Sharon L, Gangavarapu Karthik, Krause Tyler, Qiu Xiangguo, He Shinhua, Das Jishnu, Suscovich Todd J, Lai Jonathan, Chandran Kartik, Zeitlin Larry, Crowe James E, Lauffenburger Douglas, Kawaoka Yoshihiro, Kobinger Gary P, Andersen Kristian G, Dye John M, Saphire Erica Ollmann, Alter Galit
Аннотация
The recent Ebola virus (EBOV) epidemic highlighted the need for effective vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against EBOV are critical for controlling disease, and recombinant monoclonal antibodies (mAbs) can protect from infection. However, antibodies mediate an array of antiviral functions including neutralization as well as engagement of Fc-domain receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing of infected cells. Thus, to understand the antibody features mediating EBOV protection, we examined specific Fc features associated with protection using a library of EBOV-specific mAbs. Neutralization was strongly associated with therapeutic protection against EBOV. However, several neutralizing mAbs failed to protect, while several non-neutralizing or weakly neutralizing mAbs could protect. Antibody-mediated effector functions, including phagocytosis and NK cell activation, were associated with protection, particularly for antibodies with moderate neutralizing activity. This framework identifies functional correlates that can inform therapeutic and vaccine design strategies against EBOV and other pathogens.