Generation and protective efficacy of a cold-adapted attenuated avian H9N2 influenza vaccine

Abstract

To prevent H9N2 avian influenza virus infection in chickens, a long-term vaccination program using inactivated vaccines has been implemented in China. However, the protective efficacy of inactivated vaccines against antigenic drift variants is limited, and H9N2 influenza virus continues to circulate in vaccinated chicken flocks in China. Therefore, developing a cross-reactive vaccine to control the impact of H9N2 influenza in the poultry industry remains a high priority. In the present study, we developed a live cold-adapted H9N2 influenza vaccine candidate (SD/01/10-ca) by serial passages in embryonated eggs at successively lower temperatures. A total of 13 amino acid mutations occurred during the cold-adaptation of this H9N2 virus. The candidate was safe in chickens and induced robust hemagglutination-inhibition antibody responses and influenza virus–specific CD4+ and CD8+ T cell immune responses in chickens immunized intranasally. Importantly, the candidate could confer protection of chickens from homologous and heterogenous H9N2 viruses. These results demonstrated that the cold-adapted attenuated H9N2 virus would be selected as a vaccine to control the infection of prevalent H9N2 influenza viruses in chickens.

A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1

“…Contrasting the results from chickens, the riMLIV in ferrets was transmitted to direct contact animals. Further safety mechanisms, like the generation of cold-adapted mutants 41,42 and/or the introduction of species-specific siRNA targets 22,43 , could be used to improve the applicability of the prototype as a vaccine for mammalian species. Interestingly, vaccine virus genome was recorded in nasal washing fluid of one naive direct contact sentinel, and that particular animal also seroconverted at a later time point.…”

“…The current MLIVs are based on apathogenic influenza viruses, and attenuation is, e.g. achieved by using truncated NS1 proteins 21 or restricted replication capacities due to cold-adaptation 22 or the introduction of elastasespecific cleavage sites into the HA precursor protein 23 . Although cold-adapted MLIVs have been licensed for several years for use in humans, there are no MLIVs licensed for poultry yet, and only two types of vector-based live vaccines are on the market 18 .…”

Live poultry vaccines against highly pathogenic avian influenza viruses

“…Influenza virus of the H9N2 subtype also continues to circulate in vaccinated chicken flocks in China because the protective efficacy of inactivated vaccines against antigenic drift variants is limited [9]. Since the effectiveness of inactivated vaccines strongly depends on the antigenic match of the HA in the vaccine and the HA of the field virus, the antigenic diversity of avian influenza viruses has been recognized as the main challenge for the eradication of HPAIVs [9][10][11][12].…”

“…Live cold-adapted influenza vaccine candidates were developed by serial passages of H9N2 viruses in chicken embryos at low temperature. It was shown that the obtained mutant viruses protect chickens from homologous and heterologous strains of H9N2 subtype [9,40].…”

“…Since the effectiveness of inactivated vaccines strongly depends on the antigenic match of the HA in the vaccine and the HA of the field virus, the antigenic diversity of avian influenza viruses has been recognized as the main challenge for the eradication of HPAIVs [9][10][11][12].…”