A Human Anti-M2 Antibody Mediates Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Cytokine Secretion by Resting and Cytokine-Preactivated Natural Killer (NK) Cells.
The highly conserved matrix protein 2 (M2) is a good candidate for the development of a broadly protective influenza vaccine that induces long-lasting immunity. In animal models, natural killer (NK) cells have been proposed to play an important role in the protection provided by M2-based vaccines through a mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC). We investigated the ability of the human anti-M2 Ab1-10 monoclonal antibody (mAb) to activate human NK cells. They mediated ADCC against M2-expressing cells in the presence of Ab1-10 mAb. Furthermore, NK cell pro-inflammatory cytokine and chemokine secretion is also enhanced when Ab1-10 mAb is present. We also generated cytokine-preactivated NK cells and showed that they still displayed increased effector functions in the presence of Ab1-10 mAb. Thus, our study has demonstrated that human resting and cytokine-preactivated NK cells may have a very important role in the protection provided by anti-M2 Abs.
Division of Biotechnology Review and Research-I, Office of Biotechnology Products Review and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Venkateswara R
VR
Simhadri
Division of Biotechnology Review and Research-I, Office of Biotechnology Products Review and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Milena
M
Dimitrova
Division of Biotechnology Review and Research-I, Office of Biotechnology Products Review and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
John L
JL
Mariano
Immunopathology Group, BioCruces Health Research Institute, Barakaldo, Basque Country, Spain; Cell Therapy and Stem Cell Group, Basque Center for Transfusion and Human Tissues, Galdakao, Basque Country, Spain.
Olatz
O
Zenarruzabeitia
Influenza Division, National Center for Immunization and Respiratory Diseases, Center for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Weimin
W
Zhong
Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama Prefecture, Japan.
Tatsuhiko
T
Ozawa
Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama Prefecture, Japan.
Atsushi
A
Muraguchi
Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama Prefecture, Japan.
Hiroyuki
H
Kishi
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
Maryna C
MC
Eichelberger
Division of Biotechnology Review and Research-I, Office of Biotechnology Products Review and Research, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America; Immunopathology Group, BioCruces Health Research Institute, Barakaldo, Basque Country, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Basque Country, Spain.
Francisco
F
Borrego
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
D000911:Antibodies, Monoclonal; D016207:Cytokines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins