Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

Ying, Tianlei; Prabakaran, Ponraj; Du, Lanying; Shi, Wei; Feng, Yang; Wang, Yanping; Wang, Lingshu; Li, Wei; Jiang, Shibo; Dimitrov, Dimiter S.; Zhou, Tongqing

doi:10.1038/ncomms9223

Title: Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

Journal Article · Tue Sep 15 00:00:00 EDT 2015 · Nature Communications

DOI:https://doi.org/10.1038/ncomms9223· OSTI ID:1214653

Ying, Tianlei ^[1]; Prabakaran, Ponraj ^[2]; Du, Lanying ^[3]; Shi, Wei ^[4]; Feng, Yang ^[2]; Wang, Yanping ^[2]; Wang, Lingshu ^[4]; Li, Wei ^[5]; Jiang, Shibo ^[6]; Dimitrov, Dimiter S. ^[2]; Zhou, Tongqing ^[4]

Fudan Univ., Shanghai (China). Shanghai Medical College
National Inst. of Health (NIH), Frederick, MD (United States). National Cancer Inst.
New York Blood Center, New York, NY (United States). Lindsley F. Kimball Research Inst.
National Inst. of Health (NIH), Bethesda, MD (United States). National Inst. of Allergy and Infectious Diseases
Fudan Univ., Shanghai (China). Shanghai Medical College; National Inst. of Health (NIH), Frederick, MD (United States). National Cancer Inst.
Fudan Univ., Shanghai (China). Shanghai Medical College; New York Blood Center, New York, NY (United States). Lindsley F. Kimball Research Inst.

The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (~36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: W-31-109-ENG-38

OSTI ID:: 1214653

Journal Information:: Nature Communications, Vol. 6; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 90 works

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Title: Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

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