A novel method to assess antibody-dependent cell-mediated cytotoxicity against influenza A virus M2 in immunized murine models  

作　　者：Yinjie Liang Junjia Guo Zhen Li Shiyuan Liu Ting Zhang Shucai Sun Funa Lu Yuqian Zhai Wenling Wang Chuanyi Ning Wenjie Tan 

机构地区：[1]Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry,Guangxi Medical University,Nanning 530021,China [2]Key Laboratory of Biosafety,National Health Commission of the People’s Republic of China,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 102206,China [3]School of Laboratory Medicine,Wenzhou Medical University,Wenzhou 325035,China [4]School of Public Health,Baotou Medical College,Baotou 014040,China [5]Department of Nuclear Medicine,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China [6]Department of Microbiology,School of Basic Medicine,Inner Mongolia Medical University,Hohhot 010110,China

出　　处：《Biosafety and Health》2024年第3期178-185,共8页生物安全与健康（英文）

基　　金：the National Key Research and Development Program of China(2021YFC2300101).

摘　　要：The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.

关 键 词：Antibody-dependent cell-mediated cytotoxicity(ADCC) Influenza A virus(IAV) Matrix protein 2 extracellular domain(M2e) Cell line 

分 类 号：R392[医药卫生—免疫学] R-332[医药卫生—基础医学]