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

Yoshikazu Fujimoto, Yukiko Tomioka, Hiroki Takakuwa, Gen Ichiro Uechi, Toshiyo Yabuta, Kinuyo Ozaki, Haruka Suyama, Sayo Yamamoto, Masami Morimatsu, Le Quynh Mai, Tetsu Yamashiro, Toshihiro Ito, Koichi Otsuki, Etsuro Ono

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Article number000518
Pages (from-to)2104-2116
Number of pages13
JournalJournal of General Virology
Volume97
Issue number9
DOIs
Publication statusPublished - Sep 2016

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Nucleoproteins
Influenza A virus
Virus Diseases
Monoclonal Antibodies
Orthomyxoviridae
Transgenic Mice
Influenza in Birds
Antiviral Agents
H5N1 Subtype Influenza A Virus
Antibodies, Monoclonal, Humanized
Antibodies
Influenza Vaccines
Viral Proteins
Virulence
Mammals
Anti-Idiotypic Antibodies
Lymphocytes
Viruses

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

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

In: Journal of General Virology, Vol. 97, No. 9, 000518, 09.2016, p. 2104-2116.

Research output: Contribution to journalArticle

Fujimoto, Y, Tomioka, Y, Takakuwa, H, Uechi, GI, Yabuta, T, Ozaki, K, Suyama, H, Yamamoto, S, Morimatsu, M, Mai, LQ, Yamashiro, T, Ito, T, Otsuki, K & Ono, E 2016, 'Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection', Journal of General Virology, vol. 97, no. 9, 000518, pp. 2104-2116. https://doi.org/10.1099/jgv.0.000518
Fujimoto, Yoshikazu ; Tomioka, Yukiko ; Takakuwa, Hiroki ; Uechi, Gen Ichiro ; Yabuta, Toshiyo ; Ozaki, Kinuyo ; Suyama, Haruka ; Yamamoto, Sayo ; Morimatsu, Masami ; Mai, Le Quynh ; Yamashiro, Tetsu ; Ito, Toshihiro ; Otsuki, Koichi ; Ono, Etsuro. / Cross-protective potential of anti-nucleoprotein human monoclonal antibodies against lethal influenza A virus infection. In: Journal of General Virology. 2016 ; Vol. 97, No. 9. pp. 2104-2116.
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