Tsinghua team isolates potent neutralizing monoclonal antibodies against Ebola virus infection
Prof. Linqi Zhang’s team from Tsinghua University School of Medicine and Prof. Ling Chen’s team from State Key Laboratory of Respiratory Disease, Guangzhou Medical University, jointly published their recent discoveries on “Potent neutralizing monoclonal antibodies against Ebola virus infection” in Scientific Reports, describing the first protective monoclonal antibodies against Ebola virus isolated from China.
Single-particle EM reconstructions of Q206, Q314 and Q411 Fabs bound to EBOV GPdM.
Ebola virus is the etiologic agent of lethal hemorrhagic fever in humans and nonhuman primates. Since its discovery in 1976, Ebola virus has caused frequent outbreaks across Central Africa with exceedingly high mortality rate about 40%. Most notable was the unprecedented outbreak in West Africa in 2014 where the number of affected people has surpassed all the previously recorded cases combined, raising the great concerns about its pandemic potential and posing a serious threat to global health.
To control the outbreak and epidemic of infectious diseases such as Ebola, highly efficient prevention and treatment strategies are urgently needed. However, no vaccines or therapeutics have yet been approved by the regulatory agencies. Cocktail of monoclonal antibodies ZMapp, developed in the United States and Canada, was the only approved for compassionate use during the emergency situation and more clinical studies are underway for safety and efficacy analysis in human. Since the beginning of 2014 before the Ebola outbreak in West Africa, Prof. Zhang team initiated research program on antibody discovery against Ebola virus. The paper just came out in Scientific Reports, led by Dr. Qi Zhang, a postdoctoral fellow of Prof. Zhang, describing successful isolation of three potent neutralizing monoclonal antibodies Q206, Q314 and Q411 from the immunized Chinese rhesus macaque. In cooperation with Prof. Xiangguo Qiu at the Public Health Agency of Canada, Prof. Zhang team showed that these antibodies offered significant protection in a mouse model even at 48 hours after infection with Ebola live virus.
In cooperation with Prof. Ye Xiang’s group from Tsinghua University School of Medicine, Prof. Zhang team further analyzed the structure and function of isolated antibodies, revealing that antibodies Q206 and Q411 recognized a novel epitope located closely to the receptor binding region while antibody Q314 recognized the epitope on the glycan cap similar to 13C6, one of the three antibodies in the ZMapp cocktail. The three novel antibodies are independent on the complements and can neutralize almost 100% of the live Ebola virus in vitro. In the following mechanism studies, the research team confirmed that antibodies Q206 and Q411 partially interfered the interaction between the viral glycoprotein and endosomal receptor NPC1, critical for virus entry. Taken together, the three antibodies have a great potential to become candidates for future development as therapeuticas well as preventative tools against Ebola virus infection.
This project was supported by funding from the National Natural Science Foundation Award81590762 and 81530065, Ministry of Science and Technology of China (2014CB542500-03).
Paper link：http://www.nature.com/articles/srep25856
