A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza A Hemagglutinins

被引:952
作者
Corti, Davide [2 ,3 ]
Voss, Jarrod [1 ]
Gamblin, Steven J. [1 ]
Codoni, Giosiana [3 ]
Macagno, Annalisa [3 ]
Jarrossay, David [3 ]
Vachieri, Sebastien G. [1 ]
Pinna, Debora [3 ]
Minola, Andrea [3 ]
Vanzetta, Fabrizia [2 ]
Silacci, Chiara [3 ]
Fernandez-Rodriguez, Blanca M. [3 ]
Agatic, Gloria [2 ]
Bianchi, Siro [2 ]
Giacchetto-Sasselli, Isabella [3 ]
Calder, Lesley [1 ]
Sallusto, Federica [3 ]
Collins, Patrick [1 ]
Haire, Lesley F. [1 ]
Temperton, Nigel [4 ]
Langedijk, Johannes P. M. [5 ]
Skehel, John J. [1 ]
Lanzavecchia, Antonio [3 ,6 ]
机构
[1] Natl Inst Med Res, MRC, London NW7 1AA, England
[2] Humabs BioMed SA, CH-6500 Bellinzona, Switzerland
[3] Inst Res Biomed, CH-6500 Bellinzona, Switzerland
[4] Univ Kent, Sch Pharm, Viral Pseudotype Unit, Chatham ME4 4TB, Kent, England
[5] Pepscan Therapeut BV, NL-8243 RC Lelystad, Netherlands
[6] ETH, Inst Microbiol, CH-8032 Zurich, Switzerland
基金
英国医学研究理事会; 英国惠康基金; 瑞士国家科学基金会; 欧洲研究理事会;
关键词
MEMBRANE-FUSION; RECEPTOR-BINDING; MONOCLONAL-ANTIBODIES; VIRUS HEMAGGLUTININ; B-CELLS; COMPLEX; SEQUENCES; SUBTYPES; EPITOPE; SITE;
D O I
10.1126/science.1205669
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The isolation of broadly neutralizing antibodies against influenza A viruses has been a long-sought goal for therapeutic approaches and vaccine design. Using a single-cell culture method for screening large numbers of human plasma cells, we isolated a neutralizing monoclonal antibody that recognized the hemagglutinin (HA) glycoprotein of all 16 subtypes and neutralized both group 1 and group 2 influenza A viruses. Passive transfer of this antibody conferred protection to mice and ferrets. Complexes with HAs from the group 1 H1 and the group 2 H3 subtypes analyzed by x-ray crystallography showed that the antibody bound to a conserved epitope in the F subdomain. This antibody may be used for passive protection and to inform vaccine design because of its broad specificity and neutralization potency.
引用
收藏
页码:850 / 856
页数:7
相关论文
共 33 条
[1]   An antibody that prevents the hemagglutinin low pH fusogenic transition [J].
Barbey-Martin, C ;
Gigant, B ;
Bizebard, T ;
Calder, LJ ;
Wharton, SA ;
Skehel, JJ ;
Knossow, M .
VIROLOGY, 2002, 294 (01) :70-74
[2]   Cleavage of Influenza Virus Hemagglutinin by Airway Proteases TMPRSS2 and HAT Differs in Subcellular Localization and Susceptibility to Protease Inhibitors [J].
Boettcher-Friebertshaeuser, Eva ;
Freuer, Catharina ;
Sielaff, Frank ;
Schmidt, Sarah ;
Eickmann, Markus ;
Uhlendorff, Jennifer ;
Steinmetzer, Torsten ;
Klenk, Hans-Dieter ;
Garten, Wolfgang .
JOURNAL OF VIROLOGY, 2010, 84 (11) :5605-5614
[3]   STRUCTURE OF INFLUENZA HEMAGGLUTININ AT THE PH OF MEMBRANE-FUSION [J].
BULLOUGH, PA ;
HUGHSON, FM ;
SKEHEL, JJ ;
WILEY, DC .
NATURE, 1994, 371 (6492) :37-43
[4]   Structural organization of a filamentous influenza A virus [J].
Calder, Lesley J. ;
Wasilewski, Sebastian ;
Berriman, John A. ;
Rosenthal, Peter B. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (23) :10685-10690
[5]   Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals [J].
Cassese, G ;
Arce, S ;
Hauser, AE ;
Lehnert, K ;
Moewes, B ;
Mostarac, M ;
Muehlinghaus, G ;
Szyska, M ;
Radbruch, A ;
Manz, RA .
JOURNAL OF IMMUNOLOGY, 2003, 171 (04) :1684-1690
[6]   Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine [J].
Corti, Davide ;
Suguitan, Amorsolo L., Jr. ;
Pinna, Debora ;
Silacci, Chiara ;
Fernandez-Rodriguez, Blanca M. ;
Vanzetta, Fabrizia ;
Santos, Celia ;
Luke, Catherine J. ;
Torres-Velez, Fernando J. ;
Temperton, Nigel J. ;
Weiss, Robin A. ;
Sallusto, Federica ;
Subbarao, Kanta ;
Lanzavecchia, Antonio .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (05) :1663-1673
[7]   STRUCTURE AND COMPOSITION OF INFLUENZA-VIRUS - A SMALL-ANGLE NEUTRON-SCATTERING STUDY [J].
CUSACK, S ;
RUIGROK, RWH ;
KRYGSMAN, PCJ ;
MELLEMA, JE .
JOURNAL OF MOLECULAR BIOLOGY, 1985, 186 (03) :565-582
[8]   Antibody Recognition of a Highly Conserved Influenza Virus Epitope [J].
Ekiert, Damian C. ;
Bhabha, Gira ;
Elsliger, Marc-Andre ;
Friesen, Robert H. E. ;
Jongeneelen, Mandy ;
Throsby, Mark ;
Goudsmit, Jaap ;
Wilson, Ian A. .
SCIENCE, 2009, 324 (5924) :246-251
[9]   A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site [J].
Fleury, D ;
Barrère, B ;
Bizebard, T ;
Daniels, RS ;
Skehel, JJ ;
Knossow, M .
NATURE STRUCTURAL BIOLOGY, 1999, 6 (06) :530-534
[10]   Influenza Hemagglutinin and Neuraminidase Membrane Glycoproteins [J].
Gamblin, Steven J. ;
Skehel, John J. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (37) :28403-28409