%0 Journal Article %A Fujimoto, Yoshikazu %A Tomioka, Yukiko %A Takakuwa, Hiroki %A Uechi, Gen-Ichiro %A Yabuta, Toshiyo %A Ozaki, Kinuyo %A Suyama, Haruka %A Yamamoto, Sayo %A Morimatsu, Masami %A Mai, Le Quynh %A Yamashiro, Tetsu %A Ito, Toshihiro %A Otsuki, Koichi %A Ono, Etsuro %T Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection %D 2016 %J Journal of General Virology, %V 97 %N 9 %P 2104-2116 %@ 1465-2099 %R https://doi.org/10.1099/jgv.0.000518 %K antiviral effects %K H1N1 influenza virus %K Anti-nucleoprotein monoclonal antibody %K H5N1 highly pathogenic avian influenza virus %K transgenic mouse %I Microbiology Society, %X The nucleoprotein (NP) possesses regions that are highly conserved among influenza A viruses, and has therefore been one of the target viral proteins for development of a universal influenza vaccine. It has been expected that human or humanized antibodies will be made available for the prophylaxis, pre-emptive and acute treatment of viral infection. However, it is still unclear whether anti-NP human antibody can confer protection against influenza virus infection. In this study, we generated transgenic mice expressing anti-NP human mAbs derived from lymphocytes of a patient infected with H5N1 highly pathogenic avian influenza (HPAI) virus, and experimental infections were conducted to examine antiviral effects of the anti-NP antibodies against H5N1 HPAI viral infections with a high fatality rate in mammals. Transgenic mouse lines expressing the anti-NP human mAbs at more than 1 mg ml−1 showed marked resistance to H5N1 virus infections. In addition, resistance to infection with an H1N1 subtype that shows strong pathogenicity to mice was also confirmed. Although the anti-NP mAbs expressed in the transgenic mice did not neutralize the virus, the mAbs could bind to NP located on the surface of infected cells. These results suggested a possibility that the non-neutralizing anti-NP human mAbs could induce indirect antiviral effects, such as antibody-dependent cellular cytotoxicity or complement-dependent cytotoxicity. Taken together, these results demonstrated that anti-NP human mAbs play an important role in heterosubtypic protection against lethal influenza virus infections in vivo. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000518