Abstract
Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. An H7N9 vaccine is urgently needed, as a licensed human vaccine against H7N9 influenza is currently not available. Here, we developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 haemagglutinin (HA) gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. For comparison, an H7N9 DNA vaccine based on HA was also generated and tested in mice and guinea pigs. The results demonstrated that both AdC68-H7HA and the DNA vaccine prime-adenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. A post-immunization serum transfer experiment showed that antibody responses could completely protect against lethal challenge, while a T cell depletion experiment indicated that HA-specific CD8+ T cells responses also contributed to protection. Therefore, both HA-specific humoral immunity and cellular immunity play important roles in the protection. These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes.
Highlights
Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses
We compared the outcomes of the AdC68-H7HA vaccine with those of a DNA vaccine based on H7N9 HA and assessed the efficacy of a DNA prime-adenovirus boost regimen in both mouse and guinea pig models
The DNA-only group induced a lower percentage of IFN-γ-secreting CD8+ T cells owing to its poor immunogenicity. These results indicate that the adenovirus AdC68-H7HA alone and prime-boost treatments can remarkably activate T cell responses
Summary
Since 2013, the outbreak or sporadic infection of a new reassortant H7N9 influenza virus in China has resulted in hundreds of deaths and thousands of illnesses. The results demonstrated that both AdC68-H7HA and the DNA vaccine primeadenovirus boost regimen induced potent immune responses in animals and completely protected mice from lethal H7N9 influenza viral challenge. Both HA-specific humoral immunity and cellular immunity play important roles in the protection These data suggest that the chimpanzee adenovirus expressing HA is a promising vaccine candidate for H7N9 virus or other influenza viral subtypes. Live attenuated vaccines pose a risk of mutating back to the original, un-attenuated sequence[9] These clinically used seasonal influenza vaccines provide limited protection against heterogeneous influenza viral infections, such as the H5N1 and H7N9 strains[10, 11]. Live attenuated H7N9 vaccines may show good immunogenicity and can confer protection against H7N9 viral infection[13], but they may potentially re-assort with other influenza viruses owing to the segmented genome. We compared the outcomes of the AdC68-H7HA vaccine with those of a DNA vaccine based on H7N9 HA and assessed the efficacy of a DNA prime-adenovirus boost regimen in both mouse and guinea pig models
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