4.5 Article

Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir

Journal

MABS
Volume 8, Issue 6, Pages 1156-1166

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2016.1183083

Keywords

Cross-protection; highly pathogenic avian influenza virus; human monoclonal antibody; hemagglutinin; newly emerging H5 viruses; oseltamivir

Funding

  1. 12-5 Mega Project from the Ministry of Science and Technology in China [2013ZX10004003-003]
  2. Li Kai-Shing Founda-495 tion in Hong Kong

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Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1mg/kg of antibody 100F4 at 4hours before, or 20mg/kg antibody 100F4 at 72hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1mg/kg antibody 100F4 prophylactically or 10mg/kg 100F4 therapeutically outperforms a 5-day course of 10mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted.

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