@article{f5cb9ba503544348b723988d3a069749,
title = "Antibody therapy for Lassa fever",
abstract = "Serum from convalescent Lassa fever patients was previously shown to be ineffective as a source of protective antibodies in some early studies. Subsequently, monoclonal antibodies (MAbs) to the Lassa virus (LASV) glycoprotein produced by memory B cells of West African patients who survived Lassa fever were identified. Development of MAbs as potential Lassa immunotherapeutics was facilitated by structural studies and mutational analyses that identified protective epitopes on the prefusion form of the LASV glycoprotein. Human mAbs were screened for reactivity to different neutralizing epitopes, potency, and broad reactivity against multiple lineages of LASV. MAbs were downselected in a guinea pig model of Lassa fever. A cocktail of three human MAbs designated Arevirumab-3 rescued 100% of Cynomolgus macaques at advanced stages of disease more than a week post-infection. Antibody therapeutics may be further developed in clinical trials in endemic areas potentially offering a key treatment option for Lassa fever.",
author = "Cross, {Robert W.} and Hastie, {Kathryn M.} and Chad Mire and Robinson, {James E.} and Geisbert, {Thomas W.} and Branco, {Luis M.} and {Ollmann Saphire}, E. and Garry, {Robert F.}",
note = "Funding Information: This work was supported by contract HSN272200900049C from the National Institutes of Health (NIH) and by 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 . Funding Information: This work was supported by contract HSN272200900049C from the National Institutes of Health (NIH) and by NIH grants AI067188, AI067927, AI070530, AI081982, AI082119, AI082805AI088843, 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. Deborah H. Elliott, Julie A. Rouelle, Chandrika B. Kannadka, Ashley A. Smira, Courtney E. Garry, Benjamin T. Bradley, Haini Yu, and Rachael E. Yenni isolated and characterized the huMabs discussed in this review. Michelle A. Zandonatti contributed to the structural characterization of the LASV GPC trimer. Joan B. Geisbert, Viktoriya Borisevich, Krystle N. Agans, Daniel J. Deer, and Karla A. Fenton performed immunotherapeutic studies in guinea pigs and monkeys at BSL-4. Megan L. Heinrich, Megan M. Rowland, and Anatoliy P. Koval purified huMAbs for these studies. Mathew L. Boisen, Diana K. S. Nelson, and Duane J. Bush developed LASV immunoassays used to identify and characterize LASV huMAbs. Augustine Goba, Mambu Momoh, Mohamed Fullah, and John Demby Sandi characterized immune responses to LASV in Sierra Leonean patients. Donald S. Grant, S. Humarr Khan, Michael Gbakie, Mbalu Fonnie, Veronica J. Koroma, and Lansana Kanneh provided clinical care for Lassa fever patients in Sierra Leone and obtained blood for huMAb isolation from Lassa fever survivors. Christian T. Happi, Odia Ikponmwosa, Philomema Emeron, Danny A. Asogun, Peter O. Okokhere, and Onikepe O. Folarin provided clinical care for Lassa fever patients in Nigeria and obtained blood for huMAb isolation from Lassa fever survivors. John S. Schieffelin is clinical director of the Viral Hemorrhagic Fever Consortium (VHFC) and Jeffrey G. Shaffer is data manager of the VHFC; this work could not proceed without their efforts. Kayla G. Barnes, Anna E. Lachenauer, Aaron E. Lin, Mahan Nekoui, Dylan Kotliar, Sarah M. Winnicki, Danny Park, Nathan Yozwiak, Katherine J. Siddle, Matthias Pauthner, Christian T Happi, Kristian G. Andersen, and Pardis C. Sabeti defined LASV genetic diversity. Saori Sakabe, Brian Sullivan, Juan Carlos de la Torre, Stephanie Lavergne, and Michael B.A. Oldstone remind us that cellular immune responses to LASV are important for recovery from natural infection and vaccine response. Christopher M. Bishop, Tynette Hills, Lilia Melnik, Brandon Beddingfield, Andrew Hoffman, Allison Smither, Antoinette Bell, Simbirie Jalloh, and Allyson Haislip provide logistical and scientific support and program management. We also recognize the support of the Sierra Leonean Ministry of Health and Sanitation, the Nigerian Ministry of Health and other members of the VHFC not named here. We are also grateful for the contributions of Lassa fever patients, their families and communities. Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",
year = "2019",
month = aug,
doi = "10.1016/j.coviro.2019.07.003",
language = "English (US)",
volume = "37",
pages = "97--104",
journal = "Current Opinion in Virology",
issn = "1879-6257",
publisher = "Elsevier BV",
}