Cross-Reactive Influenza-Specific Antibody-Dependent Cellular Cytotoxicity Antibodies in the Absence of Neutralizing Antibodies

被引:192
作者
Jegaskanda, Sinthujan [1 ]
Job, Emma R. [1 ]
Kramski, Marit [1 ]
Laurie, Karen [2 ]
Isitman, Gamze [1 ]
de Rose, Robert [1 ]
Winnall, Wendy R. [1 ]
Stratov, Ivan [1 ]
Brooks, Andrew G. [1 ]
Reading, Patrick C. [1 ,2 ]
Kent, Stephen J. [1 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia
[2] World Hlth Org Collaborating Ctr Reference & Res, Victorian Infect Dis Reference Lab, Melbourne, Vic 3051, Australia
基金
英国医学研究理事会;
关键词
MEDIATED CYTO-TOXICITY; EXTRACELLULAR DOMAIN; ANTIGENIC DRIFT; FC-RECEPTOR; VIRUS; VACCINE; H1N1; CELLS; INFECTION; HEMAGGLUTININ;
D O I
10.4049/jimmunol.1201574
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A better understanding of immunity to influenza virus is needed to generate cross-protective vaccines. Engagement of Ab-dependent cellular cytotoxicity (ADCC) Abs by NK cells leads to killing of virus-infected cells and secretion of antiviral cytokines and chemokines. ADCC Abs may target more conserved influenza virus Ags compared with neutralizing Abs. There has been minimal interest in influenza-specific ADCC in recent decades. In this study, we developed novel assays to assess the specificity and function of influenza-specific ADCC Abs. We found that healthy influenza-seropositive young adults without detectable neutralizing Abs to the hemagglutinin of the 1968 H3N2 influenza strain (A/Aichi/2/1968) almost always had ADCC Abs that triggered NK cell activation and in vitro elimination of influenza-infected human blood and respiratory epithelial cells. Furthermore, we detected ADCC in the absence of neutralization to both the recent H1N1 pandemic strain (A/California/04/2009) as well as the avian H5N1 influenza hemagglutinin (A/Anhui/01/2005). We conclude that there is a remarkable degree of cross-reactivity of influenza-specific ADCC Abs in seropositive humans. Targeting cross-reactive influenza-specific ADCC epitopes by vaccination could lead to improved influenza vaccines. The Journal of Immunology, 2013, 190: 1837-1848.
引用
收藏
页码:1837 / 1848
页数:12
相关论文
共 58 条
[1]   Relationship between CD107a expression and cytotoxic activity [J].
Aktas, Esin ;
Kucuksezer, Umut Can ;
Bilgic, Sema ;
Erten, Gaye ;
Deniz, Gunnur .
CELLULAR IMMUNOLOGY, 2009, 254 (02) :149-154
[2]   Clinical Cancer Therapy by NK Cells via Antibody-Dependent Cell-Mediated Cytotoxicity [J].
Alderson, Kory L. ;
Sondel, Paul M. .
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY, 2011,
[3]   CD107a as a functional marker for the identification of natural killer cell activity [J].
Alter, G ;
Malenfant, JM ;
Altfeld, M .
JOURNAL OF IMMUNOLOGICAL METHODS, 2004, 294 (1-2) :15-22
[4]  
[Anonymous], 2003, Wkly Epidemiol Rec, V78, P77
[5]  
[Anonymous], 2009, INFL SEAS
[6]   A dose-response evaluation of inactivated influenza vaccine given intranasally and intramuscularly to healthy young adults [J].
Atmar, Robert L. ;
Keitel, Wendy A. ;
Cate, Thomas R. ;
Munoz, Flor M. ;
Ruben, Fred ;
Couch, Robert B. .
VACCINE, 2007, 25 (29) :5367-5373
[7]  
BUCKLEY RH, 1968, PEDIATRICS, V41, P600
[8]   Activation of NK Cells by ADCC Antibodies and HIV Disease Progression [J].
Chung, Amy W. ;
Navis, Marjon ;
Isitman, Gamze ;
Wren, Leia ;
Silvers, Julie ;
Amin, Janaki ;
Kent, Stephen J. ;
Stratov, Ivan .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2011, 58 (02) :127-131
[9]   Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure [J].
Chung, Amy W. ;
Isitman, Gamze ;
Navis, Marjon ;
Kramski, Marit ;
Center, Rob J. ;
Kent, Stephen J. ;
Stratov, Ivan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (18) :7505-7510
[10]   Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes [J].
Clara Monsalvo, Ana ;
Batalle, Juan P. ;
Florencia Lopez, M. ;
Krause, Jens C. ;
Klemenc, Jennifer ;
Zea Hernandez, Johanna ;
Maskin, Bernardo ;
Bugna, Jimena ;
Rubinstein, Carlos ;
Aguilar, Leandro ;
Dalurzo, Liliana ;
Libster, Romina ;
Savy, Vilma ;
Baumeister, Elsa ;
Aguilar, Liliana ;
Cabral, Graciela ;
Font, Julia ;
Solari, Liliana ;
Weller, Kevin P. ;
Johnson, Joyce ;
Echavarria, Marcela ;
Edwards, Kathryn M. ;
Chappell, James D. ;
Crowe, James E., Jr. ;
Williams, John V. ;
Melendi, Guillermina A. ;
Polack, Fernando P. .
NATURE MEDICINE, 2011, 17 (02) :195-U225