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Title: Rational engineering and characterization of an mAb that neutralizes Zika virus by targeting a mutationally constrained quaternary epitope
Authors: Tharakaraman, Kannan
Watanabe, Satoru
Chan, Kuan Rong
Huan, Jia
Subramanian, Vidya
Chionh, Yok Hian
Raguram, Aditya
Quinlan, Devin
McBee, Megan
Ong, Eugenia Z.
Gan, Esther S.
Tan, Hwee Cheng
Tyagi, Anu
Bhushan, Shashi
Lescar, Julien
Vasudevan, Subhash G.
Ooi, Eng Eong
Sasisekharan, Ram
Keywords: Science::Biological sciences
Issue Date: 2018
Source: Tharakaraman, K., Watanabe, S., Chan, K. R., Huan, J., Subramanian, V., Chionh, Y. H., . . . Sasisekharan, R. (2018). Rational engineering and characterization of an mAb that neutralizes Zika virus by targeting a mutationally constrained quaternary epitope. Cell Host & Mricrobe, 23(5), 618-627.e6. doi:10.1016/j.chom.2018.04.004
Journal: Cell Host & Microbe
Abstract: Following the recent emergence of Zika virus (ZIKV), many murine and human neutralizing anti-ZIKV antibodies have been reported. Given the risk of virus escape mutants, engineering antibodies that target mutationally constrained epitopes with therapeutically relevant potencies can be valuable for combating future outbreaks. Here, we applied computational methods to engineer an antibody, ZAb_FLEP, that targets a highly networked and therefore mutationally constrained surface formed by the envelope protein dimer. ZAb_FLEP neutralized a breadth of ZIKV strains and protected mice in distinct in vivo models, including resolving vertical transmission and fetal mortality in infected pregnant mice. Serial passaging of ZIKV in the presence of ZAb_FLEP failed to generate viral escape mutants, suggesting that its epitope is indeed mutationally constrained. A single-particle cryo-EM reconstruction of the Fab-ZIKV complex validated the structural model and revealed insights into ZAb_FLEP's neutralization mechanism. ZAb_FLEP has potential as a therapeutic in future outbreaks.
ISSN: 1931-3128
DOI: 10.1016/j.chom.2018.04.004
Rights: © 2018 Elsevier Inc. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles


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