Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway

PLoS Pathogens
Jianhua SuiWayne A Marasco

Abstract

Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against ...Continue Reading

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Citations

Apr 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Xian-Chun TangWayne A Marasco
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Methods Mentioned

BETA
ELISA
phage display
chip
Assay
biosensor
enzyme-linked immunoabsorbent assay
PCR
affinity purification
transfection

Software Mentioned

Biacore T100

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