A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage.

The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.

Chicken IL-7 as a potent adjuvant enhances IBDV VP2 DNA vaccine immunogenicity and protective efficacy.

Our previous work has demonstrated that the mammalian interleukin-7 (IL-7) gene can enhance the immunogenicity of DNA vaccine. Whether chicken IL-7 (chIL-7) possesses the ability to enhance the immunogenicity of VP2 DNA vaccine of infectious bursal disease virus (IBDV) remained unknown. To investigate this, we constructed a VP2 antigenic region (VP2366) gene and chIL-7 gene vectors, co-immunized chicken with these vectors and analyzed the effects of the chIL-7 gene on VP2366 gene immunogenicity. Results showed that co-administrated chIL-7 gene with VP2 DNA vaccine significantly increased specific serum antibody titers against IBDV, and enhanced lymphocyte proliferation and IFN-γ and IL-4 productions. More importantly, chIL-7 gene significantly increased VP2366 gene-induced protection against virulent IBDV infection, indicating that the chIL-7 gene possessed the capacity to enhance VP2366 DNA vaccine immunogenicity, and therefore might function as a novel adjuvant for IBDV VP2 DNA vaccine. Mechanically, chIL-7 could stimulate the common cytokine receptor γ chain (γc) expressions in vitro and in vivo, which might be involved in chIL-7 enhancement of the immunogenicity of VP2 DNA vaccine.

[Mutations of the hemagglutinin gene of H9N2 subtype avian influenza viruses under selective pressure of antibody].

OBJECTIVE: To understand mutations of avian influenza virus (AIV) under the antibody selective pressures. METHODS: We continuously passed an H9N2-AIV strain LG1 in embryos with or without maternal antibody to LG1 in 6 separate serials. At the 10th, 20th, 30th, 40th and 50th passages in each serial, H9 hemagglutinatin gene (HA) sequences were determined and compared to the original LG1 strain. RESULTS: Only unstable random mutations happened in 29 sites with nonsynonymous vs synonymous (N/S) mutation ratio of 1.42 during 50 passages in 2 serials without maternal antibodies. However, multiple stable nonsynonymous mutations were detected gradually during 50 passages of 4 serials in embryos with maternal antibody to LG1 strain, and the NS/S ratio was as high as 3.46 among 45 mutated sites. CONCLUSION: The results suggested that the antibody selective pressure influenced mutations of H9N2 AIV HA gene during the passages in embryos with maternal antibody. Embryos with maternal antibody to certain viruses could be used as experimental models to study the immune selective pressures on viral mutations.