Guiding the Immune Response against Influenza Virus Hemagglutinin toward the Conserved Stalk Domain by Hyperglycosylation of the Globular Head Domain

被引:159
作者
Eggink, Dirk [1 ]
Goff, Peter H. [1 ,2 ]
Palese, Peter [1 ,3 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY USA
[3] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA
关键词
MONOCLONAL-ANTIBODIES; GLYCOSYLATION; SITES; RECOGNITION; INDUCTION; EVOLUTION; INFECTION; SELECTION; EFFICACY; EPITOPE;
D O I
10.1128/JVI.02608-13
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Influenza virus hemagglutinin consists of a highly variable and immunodominant head domain and a more conserved but immunosubdominant stalk domain. We introduced seven N-linked glycosylation sites in the hemagglutinin head domain to shield the immunodominant antigenic sites. The hyperglycosylated hemagglutinin enhanced stalk-directed seroreactivity while dampening the head response in immunized mice. Upon influenza virus challenge, mice vaccinated with the hyperglycosylated hemagglutinin were better protected against morbidity and mortality than mice receiving the wild-type hemagglutinin.
引用
收藏
页码:699 / 704
页数:6
相关论文
共 38 条
[1]   GlyProt:: in silico glycosylation of proteins [J].
Bohne-Lang, A ;
von der Lieth, CW .
NUCLEIC ACIDS RESEARCH, 2005, 33 :W214-W219
[2]   THE ANTIGENIC STRUCTURE OF THE INFLUENZA-VIRUS A/PR/8/34 HEMAGGLUTININ (H-1 SUBTYPE) [J].
CATON, AJ ;
BROWNLEE, GG ;
YEWDELL, JW ;
GERHARD, W .
CELL, 1982, 31 (02) :417-427
[3]   Fitness costs limit influenza A virus hemagglutinin glycosylation as an immune evasion strategy [J].
Das, Suman R. ;
Hensley, Scott E. ;
David, Alexandre ;
Schmidt, Loren ;
Gibbs, James S. ;
Puigbo, Pere ;
Ince, William L. ;
Bennink, Jack R. ;
Yewdell, Jonathan W. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (51) :E1417-E1422
[4]   Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain [J].
Das, Suman R. ;
Puigbo, Pere ;
Hensley, Scott E. ;
Hurt, Darrell E. ;
Bennink, Jack R. ;
Yewdell, Jonathan W. .
PLOS PATHOGENS, 2010, 6 (11)
[5]   Glycan-Dependent Immunogenicity of Recombinant Soluble Trimeric Hemagglutinin [J].
de Vries, Robert P. ;
Smit, Cornelis H. ;
de Bruin, Erwin ;
Rigter, Alan ;
de Vries, Erik ;
Cornelissen, Lisette A. H. M. ;
Eggink, Dirk ;
Chung, Nancy P. Y. ;
Moore, John P. ;
Sanders, Rogier W. ;
Hokke, Cornelis H. ;
Koopmans, Marion ;
Rottier, Peter J. M. ;
de Haan, Cornelis A. M. .
JOURNAL OF VIROLOGY, 2012, 86 (21) :11735-11744
[6]   Partial Enzymatic Deglycosylation Preserves the Structure of Cleaved Recombinant HIV-1 Envelope Glycoprotein Trimers [J].
Depetris, Rafael S. ;
Julien, Jean-Philippe ;
Khayat, Reza ;
Lee, Jeong Hyun ;
Pejchal, Robert ;
Katpally, Umesh ;
Cocco, Nicolette ;
Kachare, Milind ;
Massi, Evan ;
David, Kathryn B. ;
Cupo, Albert ;
Marozsan, Andre J. ;
Olson, William C. ;
Ward, Andrew B. ;
Wilson, Ian A. ;
Sanders, Rogier W. ;
Moore, John P. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (29) :24239-24254
[7]  
Dinca Luminita, 1993, Viral Immunology, V6, P75, DOI 10.1089/vim.1993.6.75
[8]   Highly Conserved Protective Epitopes on Influenza B Viruses [J].
Dreyfus, Cyrille ;
Laursen, Nick S. ;
Kwaks, Ted ;
Zuijdgeest, David ;
Khayat, Reza ;
Ekiert, Damian C. ;
Lee, Jeong Hyun ;
Metlagel, Zoltan ;
Bujny, Miriam V. ;
Jongeneelen, Mandy ;
van der Vlugt, Remko ;
Lamrani, Mohammed ;
Korse, Hans J. W. M. ;
Geelen, Eric ;
Sahin, Ozcan ;
Sieuwerts, Martijn ;
Brakenhoff, Just P. J. ;
Vogels, Ronald ;
Li, Olive T. W. ;
Poon, Leo L. M. ;
Peiris, Malik ;
Koudstaal, Wouter ;
Ward, Andrew B. ;
Wilson, Ian A. ;
Goudsmit, Jaap ;
Friesen, Robert H. E. .
SCIENCE, 2012, 337 (6100) :1343-1348
[9]   A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses [J].
Ekiert, Damian C. ;
Friesen, Robert H. E. ;
Bhabha, Gira ;
Kwaks, Ted ;
Jongeneelen, Mandy ;
Yu, Wenli ;
Ophorst, Carla ;
Cox, Freek ;
Korse, Hans J. W. M. ;
Brandenburg, Boerries ;
Vogels, Ronald ;
Brakenhoff, Just P. J. ;
Kompier, Ronald ;
Koldijk, Martin H. ;
Cornelissen, Lisette A. H. M. ;
Poon, Leo L. M. ;
Peiris, Malik ;
Koudstaal, Wouter ;
Wilson, Ian A. ;
Goudsmit, Jaap .
SCIENCE, 2011, 333 (6044) :843-850
[10]   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