| Literature DB >> 30092199 |
Bronwyn M Gunn1, Wen-Han Yu2, Marcus M Karim1, Jennifer M Brannan3, Andrew S Herbert3, Anna Z Wec4, Peter J Halfmann5, Marnie L Fusco6, Sharon L Schendel6, Karthik Gangavarapu6, Tyler Krause4, Xiangguo Qiu7, Shinhua He7, Jishnu Das2, Todd J Suscovich1, Jonathan Lai4, Kartik Chandran4, Larry Zeitlin8, James E Crowe9, Douglas Lauffenburger10, Yoshihiro Kawaoka5, Gary P Kobinger11, Kristian G Andersen12, John M Dye3, Erica Ollmann Saphire13, Galit Alter14.
Abstract
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.Entities:
Keywords: Ebola virus; Fc-receptors; antibodies; effector function; immunotherapeutics; innate immunity; phagocytosis
Mesh：
Substances：
Year: 2018 PMID： 30092199 PMCID： PMC6298217 DOI： 10.1016/j.chom.2018.07.009
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023