Abstract
H5N1 influenza virus is a threat to public health worldwide. The virus can cause severe morbidity and mortality in humans. We constructed an H5N1 influenza candidate virus vaccine from the A/chicken/Guizhou/1153/2016 strain that was recommended by the World Health Organization. In this study, we designed an H5N1 chimeric influenza A/B vaccine based on a cold-adapted (ca) influenza B virus B/Vienna/1/99 backbone. We modified the ectodomain of H5N1 hemagglutinin (HA) protein, while retaining the packaging signals of influenza B virus, and then rescued a chimeric cold-adapted H5N1 candidate influenza vaccine through a reverse genetic system. The chimeric H5N1 vaccine replicated well in eggs and the Madin-Darby Canine Kidney cells. It maintained a temperature-sensitive and cold-adapted phenotype. The H5N1 vaccine was attenuated in mice. Hemagglutination inhibition (HAI) antibodies, micro-neutralizing (MN) antibodies, and IgG antibodies were induced in immunized mice, and the mucosal IgA antibody responses were detected in their lung lavage fluids. The IFN-γ-secretion and IL-4-secretion by the mouse splenocytes were induced after stimulation with the specific H5N1 HA protein. The chimeric H5N1 candidate vaccine protected mice against lethal challenge with a wild-type highly pathogenic avian H5N1 influenza virus. The chimeric H5 candidate vaccine is thus a potentially safe, attenuated, and reassortment-incompetent vaccine with circulating A viruses.
Highlights
Influenza virus H5N1 is a major pathogen related to public health concerns worldwide.H5N1 infects domestic poultry, wild birds, humans, and other mammals
We constructed an H5N1 candidate vaccine based on the WHO recommendation for H5 preparedness antigens
Gene and the other 7 master donor plasmids from the influenza B virus were co-cultured with 293T cells and Madin-Darby canine kidney (MDCK) cells using reverse genetic methods
Summary
Influenza virus H5N1 is a major pathogen related to public health concerns worldwide. H5N1 infects domestic poultry, wild birds, humans, and other mammals. It is divided into highly pathogenic avian influenza (HPAI) and low pathogenic avian influenza (LPAI). World Health Organization (WHO), the Food and Agriculture Organization of the United. Nations (FAO), and the World Organization for Animal Health (OIE) [1]. Since 1996 when HPAI H5N1 was first detected in Chinese geese [2], this virus has been detected in poultry and wild birds in more than 50 countries [3,4,5,6,7]. With increased HPAI outbreaks in poultry, the consecutive infection with the H5N1 virus in humans has increased. The first human infection by H5N1 was reported in China, Hong Kong Special Administrative
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