Many H5 and H7 subtype avian influenza vaccines are poorly immunogenic in terms of inducing hemagglutination-inhibition (HI) antibody titers. The residue 227 (H3 numbering) in the receptor binding site in the hemagglutinin (HA) is critical for the detectability of HI antibodies induced by H5 influenza vaccines. However, whether the effect of the residue 227 on immunogenicity can be generalized in different subtypes is unclear. In this study, the impact of the HA residue 227 on immunogenicity of H5N1, H5N6 and H7N9 avian influenza vaccines was evaluated in chickens. Polymorphism analysis revealed that S227 is overwhelmingly dominant in HA of the H5N1 and H7N9 subtypes, whereas this amino acid is present in a small proportion of H5N6 viruses. The H5N1, H5N6 and H7N9 vaccines harboring S227 in HA induced relatively low HI titers at week 2 post-immunization (pi) and antibody titers increased at week 3 pi. S227N substitution in these vaccines consistently enhanced HI titers significantly. Another H5N6 vaccine harboring Q227 in HA elicited a robust HI antibody response, and Q227S substitution led to a significant drop of HI titers. Cross-HI test against the wild-type and mutant viruses revealed that the amino acid at the position 227 was associated with the detectability of HI titers induced by H5 and H7 avian influenza vaccines. The results indicate an important role of the residue 227 in HA in immunogenicity of H5 and H7 subtype avian influenza vaccines in chickens. Our findings also provided useful information for vaccine seed virus selection and genetic engineering for immunogenicity enhancement of avian influenza vaccines.
Role of the hemagglutinin residue 227 in immunogenicity of H5 and H7 subtype avian influenza vaccines in chickens
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Zenglei Hu, Yongzhong Cao, Xiufan Liu, Lei Shi, Jiangyan Zhao, Han Gu, Jiao Hu, Xiaoquan Wang, Xiaowen Liu, Shunlin Hu, Min Gu; Role of the hemagglutinin residue 227 in immunogenicity of H5 and H7 subtype avian influenza vaccines in chickens. Avian Dis doi: https://doi.org/10.1637/aviandiseases-D-20-00013
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