Abstract
In early spring 2013, the emergence of the influenza A (H7N9) virus in humans in Eastern China raised concerns of a new influenza pandemic. Development of a safe and effective H7N9 influenza vaccine is urgently needed. To this end, we first synthesized the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza A (H7N9) virus A/AnHui/1/2013. Using reverse genetics, we rescued a reassortant virus (H7N9/PR8) that contained the HA and NA genes from wild-type H7N9 and six genes encoding internal proteins from the A/Puerto Rico/8/34 (PR8) virus. Next, the pathogenicity of the reassortant virus was evaluated both in vivo and in vitro. We found that the virus was non-pathogenic in mice and was stable after serial passaging in eggs. Furthermore, we found that a monovalent influenza A (H7N9) split vaccine prepared from the virus was immunogenic in mice and ferrets. When given intramuscularly, the vaccine (two doses of at least 15-µg) completely protected mice from normally lethal wild-type H7N9 virus challenge. In summary, our H7N9 vaccine, developed over a short time, is a potential candidate for further clinical evaluation and human use.
Highlights
On 31 March 2013, the Chinese National Health and Family Planning Commission announced the occurrence of three cases of human infection with influenza A (H7N9) [1,2]
We report on the creation of an H7N9 influenza vaccine candidate virus using reverse genetics
Reverse genetics, used to generate influenza virus from cells co-transfected with plasmids carrying individual influenza virus genes, has been used in vaccine development since 1996 [6,16,17,18]
Summary
On 31 March 2013, the Chinese National Health and Family Planning Commission announced the occurrence of three cases of human infection with influenza A (H7N9) [1,2]. As of 26 May 2013, a total of 135 human cases of influenza A (H7N9) infection had been reported, including 44 deaths. The epidemiological link between the presence of the H7N9 virus in poultry and the appearance thereof in humans in 2013 implied that influenza H7N9 viruses might be directly transmitted from birds to humans. Control of the H7N9 outbreak was achieved by closing the live-bird markets of China, this episode has shown that our capability to deal with emerging influenza threats is inadequate. In addition to active management measures, the development of an H7N9 vaccine is urgently needed to protect humans from the threat of an H7N9 influenza epidemic or pandemic [5]
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