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Nat Commun. 2016 May 10;7:11544. doi: 10.1038/ncomms11544.

Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits.

Author information

1
Section of Infectious Disease, Department of Pediatrics, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
2
Department of Immunology and Microbial Science, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
3
Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, 301 University Boulevard, Galveston, Texas 77555, USA.
4
Department of Microbiology and Immunology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
5
Autoimmune Technologies, LLC, 1010 Common St #1705, New Orleans, Louisiana 70112, USA.
6
Department of Biostatistics and Bioinformatics, Tulane School of Public Health and Tropical Medicine, New Orleans, Louisiana 70112, USA.
7
Corgenix, Inc., 11575 Main Street #400, Broomfield, Colorado 80020, USA.
8
Zalgen Labs, LLC, 20271 Goldenrod Lane, Suite 2083, Germantown, Maryland 20876, USA.
9
Department of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642, USA.
10
Viral Hemorrhagic Fever Program, Kenema Government Hospital, 1 Combema Road, Kenema, Sierra Leone.
11
Department of Laboratory Sciences Polytechnic College, 2 Combema Road, Kenema, Sierra Leone.
12
Ministry of Health and Sanitation, 4th Floor Youyi Building, Freetown, Sierra Leone.
13
Department of Medicine, Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Km. 87, Benin/Auchi Road, Irrua, Nigeria.
14
Department of Biological Sciences, College of Natural Sciences, Redeemer's University, Off Gbongan-Oshogbo Road, Ede, Nigeria.
15
African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemer's University, Off Gbongan-Oshogbo Road, Ede, Nigeria.
16
Section of Infectious Disease, Department of Internal Medicine, Tulane University School of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, Louisiana 70112, USA.
17
Department of Organismic and Evolutionary Biology, Center for Systems Biology, Harvard University, 1350 Massachusetts Avenue, Cambridge, Massachusetts 02138, USA.
18
Center for Systems Biology, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
19
Department of Immunology and Infectious Disease, Harvard School of Public Health, 677 Huntington Avenue, Boston, Massachusetts 02115, USA.
20
Department of Medicine, University of Sierra Leone, Freetown, Sierra Leone.
21
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Abstract

Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition. Notably, of the 16 mAbs that neutralize LASV, 13 require the assembled glycoprotein complex for binding, while the remaining 3 require GP1 only. Compared with non-neutralizing mAbs, neutralizing mAbs have higher binding affinities and greater divergence from germline progenitors. Some mAbs potently neutralize all four LASV lineages. These insights from LASV human mAb characterization will guide strategies for immunotherapeutic development and vaccine design.

PMID:
27161536
PMCID:
PMC4866400
DOI:
10.1038/ncomms11544
[Indexed for MEDLINE]
Free PMC Article

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