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Sci Rep. 2016 May 16;6:25856. doi: 10.1038/srep25856.

Potent neutralizing monoclonal antibodies against Ebola virus infection.

Author information

1
Comprehensive AIDS Research Center, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
2
Beijing Advanced Innovation Center for Structure Biology, and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Tsinghua University, Beijing 100084, China.
3
State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China.
4
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, R3E 3R2 Canada.
5
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, R3E 0J9 Canada.
6
Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
7
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology and Research Network of Immunity and Health, and Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.

Abstract

Ebola virus infections cause a deadly hemorrhagic disease for which no vaccines or therapeutics has received regulatory approval. Here we show isolation of three (Q206, Q314 and Q411) neutralizing monoclonal antibodies (mAbs) against the surface glycoprotein (GP) of Ebola virus identified in West Africa in 2014 through sequential immunization of Chinese rhesus macaques and antigen-specific single B cell sorting. These mAbs demonstrated potent neutralizing activities against both pseudo and live Ebola virus independent of complement. Biochemical, single particle EM, and mutagenesis analysis suggested Q206 and Q411 recognized novel epitopes in the head while Q314 targeted the glycan cap in the GP1 subunit. Q206 and Q411 appeared to influence GP binding to its receptor NPC1. Treatment with these mAbs provided partial but significant protection against disease in a mouse model of Ebola virus infection. These novel mAbs could serve as promising candidates for prophylactic and therapeutic interventions against Ebola virus infection.

PMID:
27181584
PMCID:
PMC4867612
DOI:
10.1038/srep25856
[Indexed for MEDLINE]
Free PMC Article

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