Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection
Fujimoto, Yoshikazu and Tomioka, Yukiko and Takakuwa, Hiroki and Uechi, Gen-Ichiro and Yabuta, Toshiyo and Ozaki, Kinuyo and Suyama, Haruka and Yamamoto, Sayo and Morimatsu, Masami and Mai, Le Quynh and Yamashiro, Tetsu and Ito, Toshihiro and Otsuki, Koichi and Ono, Etsuro,, 97, 2104-2116 (2016),
doi = https://doi.org/10.1099/jgv.0.000518,
publicationName = Microbiology Society,
issn = 0022-1317,
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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