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

James E. Robinson (), Kathryn M. Hastie, Robert W. Cross, Rachael E. Yenni, Deborah H. Elliott, Julie A. Rouelle, Chandrika B. Kannadka, Ashley A. Smira, Courtney E. Garry, Benjamin T. Bradley, Haini Yu, Jeffrey G. Shaffer, Matt L. Boisen, Jessica N. Hartnett, Michelle A. Zandonatti, Megan M. Rowland, Megan L. Heinrich, Luis Martínez-Sobrido, Benson Cheng, Juan C. de la Torre, Kristian G. Andersen, Augustine Goba, Mambu Momoh, Mohamed Fullah, Michael Gbakie, Lansana Kanneh, Veronica J. Koroma, Richard Fonnie, Simbirie C. Jalloh, Brima Kargbo, Mohamed A. Vandi, Momoh Gbetuwa, Odia Ikponmwosa, Danny A. Asogun, Peter O. Okokhere, Onikepe A. Follarin, John S. Schieffelin, Kelly R. Pitts, Joan B. Geisbert, Peter C. Kulakoski, Russell B. Wilson, Christian T. Happi, Pardis C. Sabeti, Sahr M. Gevao, S. Humarr Khan, Donald S. Grant, Thomas W. Geisbert, Erica Ollmann Saphire, Luis M. Branco and Robert F. Garry
Additional contact information
James E. Robinson: Section of Infectious Disease, Tulane University School of Medicine
Kathryn M. Hastie: Scripps Research Institute
Robert W. Cross: University of Texas Medical Branch at Galveston
Rachael E. Yenni: Tulane University School of Medicine
Deborah H. Elliott: Section of Infectious Disease, Tulane University School of Medicine
Julie A. Rouelle: Section of Infectious Disease, Tulane University School of Medicine
Chandrika B. Kannadka: Section of Infectious Disease, Tulane University School of Medicine
Ashley A. Smira: Section of Infectious Disease, Tulane University School of Medicine
Courtney E. Garry: Section of Infectious Disease, Tulane University School of Medicine
Benjamin T. Bradley: Section of Infectious Disease, Tulane University School of Medicine
Haini Yu: Section of Infectious Disease, Tulane University School of Medicine
Jeffrey G. Shaffer: Tulane School of Public Health and Tropical Medicine
Matt L. Boisen: Corgenix, Inc.
Jessica N. Hartnett: Tulane University School of Medicine
Michelle A. Zandonatti: Scripps Research Institute
Megan M. Rowland: Zalgen Labs, LLC
Megan L. Heinrich: Zalgen Labs, LLC
Luis Martínez-Sobrido: University of Rochester
Benson Cheng: University of Rochester
Juan C. de la Torre: Scripps Research Institute
Kristian G. Andersen: Scripps Research Institute
Augustine Goba: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Mambu Momoh: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Mohamed Fullah: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Michael Gbakie: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Lansana Kanneh: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Veronica J. Koroma: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Richard Fonnie: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Simbirie C. Jalloh: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Brima Kargbo: Ministry of Health and Sanitation
Mohamed A. Vandi: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Momoh Gbetuwa: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Odia Ikponmwosa: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital
Danny A. Asogun: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital
Peter O. Okokhere: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital
Onikepe A. Follarin: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital
John S. Schieffelin: Section of Infectious Disease, Tulane University School of Medicine
Kelly R. Pitts: Corgenix, Inc.
Joan B. Geisbert: University of Texas Medical Branch at Galveston
Peter C. Kulakoski: Autoimmune Technologies, LLC, 1010 Common St #1705
Russell B. Wilson: Autoimmune Technologies, LLC, 1010 Common St #1705
Christian T. Happi: Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital
Pardis C. Sabeti: Center for Systems Biology, Harvard University
Sahr M. Gevao: University of Sierra Leone
S. Humarr Khan: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Donald S. Grant: Viral Hemorrhagic Fever Program, Kenema Government Hospital
Thomas W. Geisbert: University of Texas Medical Branch at Galveston
Erica Ollmann Saphire: Scripps Research Institute
Luis M. Branco: Zalgen Labs, LLC
Robert F. Garry: Tulane University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11544

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