Seiya Yamayoshi1, Mutsumi Ito1, Ryuta Uraki1, Tadahiro Sasaki2, Kazuyoshi Ikuta2, Yoshihiro Kawaoka3. 1. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan. 2. Department of Virology, Research Institute for Microbial Diseases, Osaka University, Japan. 3. Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Japan; Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, USA; Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Japan; ERATO Infection-Induced Host Responses Project, Japan Science and Technology Agency, Japan. Electronic address: yoshihiro.kawaoka@wisc.edu.
Abstract
OBJECTIVES: Broadly reactive human monoclonal antibodies against the HA stem of influenza A virus are being developed as therapeutic agents as well as to understand the epitopes that are essential for a universal influenza virus vaccine. METHODS: We isolated and characterized two hetero-reactive human monoclonal antibodies from an H3N2 virus-infected human. RESULTS: These antibodies, which are predominantly bound to the HA stem of group 2 HAs, used IGHV3-66 and IGHV4-38-2 germline genes, respectively. They possessed in vitro neutralizing ability, and in vivo protective efficacy against lethal infection with H3N2 or H7N9 virus. Escape mutations revealed that one of the protective antibodies recognized the α-helix A of HA2, and the other recognized the C-terminal portion of the fusion peptide and the β-sheet that precedes the α-helix A of HA2. CONCLUSIONS: Of many human protective monoclonal antibodies against the HA stem, two human protective monoclonal antibodies were isolated in this study that predominantly recognize epitopes on the HA stem of group 2 and use unique IGHV3-66 and IGHV4-38-2 germline genes.
OBJECTIVES: Broadly reactive human monoclonal antibodies against the HA stem of influenza A virus are being developed as therapeutic agents as well as to understand the epitopes that are essential for a universal influenza virus vaccine. METHODS: We isolated and characterized two hetero-reactive human monoclonal antibodies from an H3N2 virus-infected human. RESULTS: These antibodies, which are predominantly bound to the HA stem of group 2 HAs, used IGHV3-66 and IGHV4-38-2 germline genes, respectively. They possessed in vitro neutralizing ability, and in vivo protective efficacy against lethal infection with H3N2 or H7N9 virus. Escape mutations revealed that one of the protective antibodies recognized the α-helix A of HA2, and the other recognized the C-terminal portion of the fusion peptide and the β-sheet that precedes the α-helix A of HA2. CONCLUSIONS: Of many human protective monoclonal antibodies against the HA stem, two human protective monoclonal antibodies were isolated in this study that predominantly recognize epitopes on the HA stem of group 2 and use unique IGHV3-66 and IGHV4-38-2 germline genes.
Authors: Damian C Ekiert; Robert H E Friesen; Gira Bhabha; Ted Kwaks; Mandy Jongeneelen; Wenli Yu; Carla Ophorst; Freek Cox; Hans J W M Korse; Boerries Brandenburg; Ronald Vogels; Just P J Brakenhoff; Ronald Kompier; Martin H Koldijk; Lisette A H M Cornelissen; Leo L M Poon; Malik Peiris; Wouter Koudstaal; Ian A Wilson; Jaap Goudsmit Journal: Science Date: 2011-07-07 Impact factor: 47.728
Authors: Gui-Mei Li; Christopher Chiu; Jens Wrammert; Megan McCausland; Sarah F Andrews; Nai-Ying Zheng; Jane-Hwei Lee; Min Huang; Xinyan Qu; Srilatha Edupuganti; Mark Mulligan; Suman R Das; Jonathan W Yewdell; Aneesh K Mehta; Patrick C Wilson; Rafi Ahmed Journal: Proc Natl Acad Sci U S A Date: 2012-05-21 Impact factor: 11.205
Authors: M Gordon Joyce; Adam K Wheatley; Paul V Thomas; Gwo-Yu Chuang; Cinque Soto; Robert T Bailer; Aliaksandr Druz; Ivelin S Georgiev; Rebecca A Gillespie; Masaru Kanekiyo; Wing-Pui Kong; Kwanyee Leung; Sandeep N Narpala; Madhu S Prabhakaran; Eun Sung Yang; Baoshan Zhang; Yi Zhang; Mangaiarkarasi Asokan; Jeffrey C Boyington; Tatsiana Bylund; Sam Darko; Christopher R Lees; Amy Ransier; Chen-Hsiang Shen; Lingshu Wang; James R Whittle; Xueling Wu; Hadi M Yassine; Celia Santos; Yumiko Matsuoka; Yaroslav Tsybovsky; Ulrich Baxa; James C Mullikin; Kanta Subbarao; Daniel C Douek; Barney S Graham; Richard A Koup; Julie E Ledgerwood; Mario Roederer; Lawrence Shapiro; Peter D Kwong; John R Mascola; Adrian B McDermott Journal: Cell Date: 2016-07-21 Impact factor: 41.582
Authors: Irina Margine; Rong Hai; Randy A Albrecht; Gerlinde Obermoser; A Carson Harrod; Jacques Banchereau; Karolina Palucka; Adolfo García-Sastre; Peter Palese; John J Treanor; Florian Krammer Journal: J Virol Date: 2013-02-13 Impact factor: 5.103
Authors: Ali H Ellebedy; Florian Krammer; Gui-Mei Li; Matthew S Miller; Christopher Chiu; Jens Wrammert; Cathy Y Chang; Carl W Davis; Megan McCausland; Rivka Elbein; Srilatha Edupuganti; Paul Spearman; Sarah F Andrews; Patrick C Wilson; Adolfo García-Sastre; Mark J Mulligan; Aneesh K Mehta; Peter Palese; Rafi Ahmed Journal: Proc Natl Acad Sci U S A Date: 2014-08-25 Impact factor: 11.205
Authors: Jens Wrammert; Dimitrios Koutsonanos; Gui-Mei Li; Srilatha Edupuganti; Jianhua Sui; Michael Morrissey; Megan McCausland; Ioanna Skountzou; Mady Hornig; W Ian Lipkin; Aneesh Mehta; Behzad Razavi; Carlos Del Rio; Nai-Ying Zheng; Jane-Hwei Lee; Min Huang; Zahida Ali; Kaval Kaur; Sarah Andrews; Rama Rao Amara; Youliang Wang; Suman Ranjan Das; Christopher David O'Donnell; Jon W Yewdell; Kanta Subbarao; Wayne A Marasco; Mark J Mulligan; Richard Compans; Rafi Ahmed; Patrick C Wilson Journal: J Exp Med Date: 2011-01-10 Impact factor: 14.307