An SH, Hong SM, Song JH, Son SE, Lee CY, Choi KS,. Engineering an Optimal Y280-Lineage H9N2 Vaccine Strain by Tuning PB2 Activity. Int J Mol Sci. 2023 May 16;24(10):8840
H9N2 avian influenza A viruses (AIVs) cause economic losses in the poultry industry and provide internal genomic segments for the evolution of H5N1 and H7N9 AIVs into more detrimental strains for poultry and humans. In addition to the endemic Y439/Korea-lineage H9N2 viruses, the Y280-lineage spread to Korea since 2020. Conventional recombinant H9N2 vaccine strains, which bear mammalian pathogenic internal genomes of the PR8 strain, are pathogenic in BALB/c mice. To reduce the mammalian pathogenicity of the vaccine strains, the PR8 PB2 was replaced with the non-pathogenic and highly productive PB2 of the H9N2 vaccine strain 01310CE20. However, the 01310CE20 PB2 did not coordinate well with the hemagglutinin (HA) and neuraminidase (NA) of the Korean Y280-lineage strain, resulting in a 10-fold lower virus titer compared to the PR8 PB2. To increase the virus titer, the 01310CE20 PB2 was mutated (I66M-I109V-I133V) to enhance the polymerase trimer integrity with PB1 and PA, which restored the decreased virus titer without causing mouse pathogenicity. The reverse mutation (L226Q) of HA, which was believed to decrease mammalian pathogenicity by reducing mammalian receptor affinity, was verified to increase mouse pathogenicity and change antigenicity. The monovalent Y280-lineage oil emulsion vaccine produced high antibody titers for homologous antigens but undetectable titers for heterologous (Y439/Korea-lineage) antigens. However, this defect was corrected by the bivalent vaccine. Therefore, the balance of polymerase and HA/NA activities can be achieved by fine-tuning PB2 activity, and a bivalent vaccine may be more effective in controlling concurrent H9N2 viruses with different antigenicities.
See Also:
Latest articles in those days:
- Epidemiology and genetic characterization of influenza viruses circulating in Bhutan in 2022 2 days ago
- Generation of antigen-specific memory CD4 T cells by heterologous immunization enhances the magnitude of the germinal center response upon influenza infection 2 days ago
- Genomic characterization of highly pathogenic H5 avian influenza viruses from Alaska during 2022 provides evidence for genotype-specific trends of spatiotemporal and interspecies dissemination 2 days ago
- CircRNA based multivalent neuraminidase vaccine induces broad protection against influenza viruses in mice 2 days ago
- Detection and subtyping of influenza A virus in porcine clinical samples from Spain in 2020 3 days ago
[Go Top] [Close Window]