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. 2016 Sep;97(9):2104-2116.
doi: 10.1099/jgv.0.000518. Epub 2016 Jun 3.

Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection

Yoshikazu Fujimoto  1   2 , Yukiko Tomioka  3 , Hiroki Takakuwa  4 , Gen-Ichiro Uechi  5 , Toshiyo Yabuta  4 , Kinuyo Ozaki  2 , Haruka Suyama  2 , Sayo Yamamoto  2 , Masami Morimatsu  6 , Le Quynh Mai  7 , Tetsu Yamashiro  5 , Toshihiro Ito  3 , Koichi Otsuki  3   4 , Etsuro Ono  3   2   1
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Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection

Yoshikazu Fujimoto et al. J Gen Virol. 2016 Sep.

Abstract

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.

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