@article{6893bcf2829b4e6398d0a7acf814cc91,
title = "Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits",
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.",
author = "Robinson, {James E.} and Hastie, {Kathryn M.} and Cross, {Robert W.} and Yenni, {Rachael E.} and Elliott, {Deborah H.} and Rouelle, {Julie A.} and Kannadka, {Chandrika B.} and Smira, {Ashley A.} and Garry, {Courtney E.} and Bradley, {Benjamin T.} and Haini Yu and Shaffer, {Jeffrey G.} and Boisen, {Matt L.} and Hartnett, {Jessica N.} and Zandonatti, {Michelle A.} and Rowland, {Megan M.} and Heinrich, {Megan L.} and Luis Martinez-Sobrido and Benson Cheng and {De La Torre}, {Juan C.} and Andersen, {Kristian G.} and Augustine Goba and Mambu Momoh and Mohamed Fullah and Michael Gbakie and Lansana Kanneh and Koroma, {Veronica J.} and Richard Fonnie and Jalloh, {Simbirie C.} and Brima Kargbo and Vandi, {Mohamed A.} and Momoh Gbetuwa and Odia Ikponmwosa and Asogun, {Danny A.} and Okokhere, {Peter O.} and Follarin, {Onikepe A.} and Schieffelin, {John S.} and Pitts, {Kelly R.} and Geisbert, {Joan B.} and Kulakoski, {Peter C.} and Wilson, {Russell B.} and Happi, {Christian T.} and Sabeti, {Pardis C.} and Gevao, {Sahr M.} and Khan, {S. Humarr} and Grant, {Donald S.} and Geisbert, {Thomas W.} and Saphire, {Erica Ollmann} and Branco, {Luis M.} and Garry, {Robert F.}",
note = "Funding Information: This work was supported by contract HSN272200900049C from the National Institutes of Health under the B cell Epitope Discovery and Mechanisms of Antibody Protection programme (BAA-NIAID-DAIT-NIHAI2008031). Additional support came from NIH grants AI067188, AI067927, AI070530, AI081982, AI082119, AI082805 AI088843, AI104216, AI104621, AI115754, P20GM103501 and 1U01HG007480-01, and grants from the World Bank, the Bill and Melinda Gates Foundation and the Paul G. Allen Family Foundation. We also recognize the support of the Sierra Leonean Ministry of Health and Sanitation and the Nigerian Ministry of Health. Additional members of the Viral Hemorrhagic Fever Consortium (vhfc.org) who contributed to this study are listed in Supplementary Note 1. This study would not have been possible without the cooperation of Lassa fever patients presenting to Kenema Government Hospital and Irrua Specialist Teaching Hospital and their families. We dedicate this paper to Mohamed Fullah and Dr Sheik Humarr Khan, and other members of the Sierra Leone team that contracted fatal Ebola while providing health services or care to their fellow citizens.",
year = "2016",
month = may,
day = "10",
doi = "10.1038/ncomms11544",
language = "English (US)",
volume = "7",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}