HA蛋白S227N突变对H7N9亚型禽流感病毒生物学特性与疫苗免疫原性的影响

Effect of S227N substitution in the hemagglutinin on the biological characteristics and immunogenicity of H7N9 avian influenza virus

某些种类H7N9亚型禽流感疫苗诱导的血凝抑制(HI)抗体较低,可能与诊断抗原受体结合特性和HI试验的敏感性有关。本研究主要评价H7N9亚型禽流感病毒(AIV)HA蛋白受体结合区第227位丝氨酸(S)到天冬氨酰(N)的突变对病毒复制、受体结合特性与免疫原性的影响。结果显示,S227N突变对H7N9亚型AIV的复制性能无明显影响,可显著降低病毒与α-2,3及α-2,6唾液酸受体的亲和力,并导致该位点在HA蛋白表面构象改变。此外,S227N突变显著提高HI试验的敏感性与H7N9亚型灭活疫苗诱导的HI抗体滴度,对H7N9亚型免疫血清的交叉反应性无明显影响。结果表明,HA S227N突变可改变H7N9亚型AIV的受体结合特性、提高HI试验的敏感性、增强H7N9亚型疫苗的免疫原性。研究结果对于H7N9亚型禽流感疫苗免疫原性的改善及疫苗的临床评价有重要参考意义。

Some types of H7 N9 avian influenza vaccines are poorly immunogenic, which may be associated with the receptor binding specificity of the diagnostic antigen and the sensitivity of HI assay.In this study, the effect of S227 N substitution in the HA protein on virus replication, receptor binding specificity and immunogenicity of H7 N9 subtype avian influenza virus(AIV) was evaluated.The results showed that S227 N substitution had no significant impact on virus replication but markedly decreased the binding affinity with α-2,3 and α-2,6 sialic acid receptors.This substitution also resulted in the alteration of HA conformation.In addition, S227 N substitution significantly enhanced the sensitivity of HI assay and HI antibody titers induced by inactivated H7 N9 vaccine in chickens.More importantly,this substitution did not change cross-reactivity of H7 N9 antisera with different H7 N9 field strains.In conclusion,S227 Nsubstitution in HA can change the receptor binding affinity with H7 N9 virus,increase the sensitivity of HI assay and significantly enhance HI antibody titers elicited by H7 N9 vaccines.The results provide useful information for optimization and clinical evaluation of H7 N9 vaccines.