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PLoS One. 2015 Apr 27;10(4):e0124677. doi: 10.1371/journal.pone.0124677. eCollection 2015.

A Human Anti-M2 Antibody Mediates Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Cytokine Secretion by Resting and Cytokine-Preactivated Natural Killer (NK) Cells.

Author information

1
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.
2
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.
3
Influenza Division, National Center for Immunization and Respiratory Diseases, Center for Disease Control and Prevention, Atlanta, Georgia, United States of America.
4
Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama Prefecture, Japan.
5
Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, United States of America.
6
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.

Abstract

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.

PMID:
25915748
PMCID:
PMC4411161
DOI:
10.1371/journal.pone.0124677
[Indexed for MEDLINE]
Free PMC Article

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