Simhadri Venkateswara R, Dimitrova Milena, Mariano John L, Zenarruzabeitia Olatz, Zhong Weimin, Ozawa Tatsuhiko, Muraguchi Atsushi, Kishi Hiroyuki, Eichelberger Maryna C, Borrego Francisco
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; Cell Therapy and Stem Cell Group, Basque Center for Transfusion and Human Tissues, Galdakao, Basque Country, Spain.
PLoS One. 2015 Apr 27;10(4):e0124677. doi: 10.1371/journal.pone.0124677. eCollection 2015.
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.
高度保守的基质蛋白2（M2）是开发能诱导持久免疫力的广谱保护性流感疫苗的良好候选对象。在动物模型中，自然杀伤（NK）细胞被认为通过抗体依赖性细胞介导的细胞毒性（ADCC）机制在基于M2的疫苗所提供的保护中发挥重要作用。我们研究了人抗M2 Ab1-10单克隆抗体（mAb）激活人NK细胞的能力。在存在Ab1-10 mAb的情况下，它们介导了针对表达M2的细胞的ADCC。此外，当存在Ab1-10 mAb时，NK细胞促炎细胞因子和趋化因子的分泌也会增强。我们还生成了细胞因子预激活的NK细胞，并表明在存在Ab1-10 mAb的情况下它们仍表现出增强的效应功能。因此，我们的研究表明，人静息和细胞因子预激活的NK细胞可能在抗M2抗体提供的保护中发挥非常重要的作用。
