scholarly journals Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins

2019 ◽  
Vol 15 (11) ◽  
pp. e1008061 ◽  
Author(s):  
Jose A. Quiroz ◽  
Ryan J. Malonis ◽  
Larissa B. Thackray ◽  
Courtney A. Cohen ◽  
Jesper Pallesen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Human Monoclonal Antibodies

scholarly journals Chikungunya Virus Envelope-Specific Human Monoclonal Antibodies with Broad Neutralization Potency

2011 ◽  
Vol 186 (5) ◽  
pp. 3258-3264 ◽  
Author(s):  
Lucile Warter ◽  
Chia Yin Lee ◽  
Rekha Thiagarajan ◽  
Marc Grandadam ◽  
Serge Lebecque ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Human Monoclonal Antibodies ◽  
Virus Envelope

scholarly journals Use of Human Monoclonal Antibodies to Treat Chikungunya Virus Infection

2012 ◽  
Vol 207 (2) ◽  
pp. 319-322 ◽  
Author(s):  
Jan Fric ◽  
Sébastien Bertin-Maghit ◽  
Cheng-I Wang ◽  
Alessandra Nardin ◽  
Lucile Warter
Keyword(s):  
Monoclonal Antibodies ◽  
Virus Infection ◽  
Chikungunya Virus ◽  
Human Monoclonal Antibodies

scholarly journals Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus

2015 ◽  
Vol 18 (1) ◽  
pp. 86-95 ◽  
Author(s):  
Scott A. Smith ◽  
Laurie A. Silva ◽  
Julie M. Fox ◽  
Andrew I. Flyak ◽  
Nurgun Kose ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Therapeutic Activity ◽  
Human Monoclonal Antibodies ◽  
Isolation And Characterization

scholarly journals Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus

2015 ◽  
Vol 18 (3) ◽  
pp. 382 ◽  
Author(s):  
Scott A. Smith ◽  
Laurie A. Silva ◽  
Julie M. Fox ◽  
Andrew I. Flyak ◽  
Nurgun Kose ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Therapeutic Activity ◽  
Human Monoclonal Antibodies ◽  
Isolation And Characterization

scholarly journals Cryo-EM structures elucidate neutralizing mechanisms of anti-chikungunya human monoclonal antibodies with therapeutic activity

2015 ◽  
Vol 112 (45) ◽  
pp. 13898-13903 ◽  
Author(s):  
Feng Long ◽  
Rachel H. Fong ◽  
Stephen K. Austin ◽  
Zhenguo Chen ◽  
Thomas Klose ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Structural Basis ◽  
Binding Studies ◽  
Viral Glycoprotein ◽  
Human Monoclonal Antibodies ◽  
Human Mabs ◽  
Alanine Scanning Mutagenesis ◽  
Viral Surface ◽  
Fusion Loop

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes severe acute and chronic disease in humans. Although highly inhibitory murine and human monoclonal antibodies (mAbs) have been generated, the structural basis of their neutralizing activity remains poorly characterized. Here, we determined the cryo-EM structures of chikungunya virus-like particles complexed with antibody fragments (Fab) of two highly protective human mAbs, 4J21 and 5M16, that block virus fusion with host membranes. Both mAbs bind primarily to sites within the A and B domains, as well as to the B domain’s β-ribbon connector of the viral glycoprotein E2. The footprints of these antibodies on the viral surface were consistent with results from loss-of-binding studies using an alanine scanning mutagenesis-based epitope mapping approach. The Fab fragments stabilized the position of the B domain relative to the virus, particularly for the complex with 5M16. This finding is consistent with a mechanism of neutralization in which anti-CHIKV mAbs that bridge the A and B domains impede movement of the B domain away from the underlying fusion loop on the E1 glycoprotein and therefore block the requisite pH-dependent fusion of viral and host membranes.

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