Imprinting of Repeated Influenza A/H3 Exposures on Antibody Quantity and Antibody Quality: Implications for Seasonal Vaccine Strain Selection and Vaccine Performance
Imprinting of Repeated Influenza A/H3 Exposures on Antibody Quantity and Antibody Quality: Implications for Seasonal Vaccine Strain Selection and Vaccine Performance
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DOI：
10.1093/cid/ciy327
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发表时间：
2018-11-15
影响因子：
11.8
通讯作者：
Xie, Hang
中科院分区：
文献类型：
--
作者：
Kosikova, Martina;Li, Lei;Xie, Hang
背景。在每年重复接种疫苗的个体中观察到季节性流感疫苗有效性（VE）降低。还发现先前存在的流感抗体水平与疫苗接种后滴度呈负相关。这些报告表明，预先存在的免疫力可能会影响当代季节性疫苗的性能。方法。通过血凝抑制 (I IAI) 测定评估来自具有或不具有预先存在免疫力的人类的疫苗接种后血清的 A/H3 流感特异性交叉反应性。反复暴露于 H3 诱导的雪貂抗血清也进行了 HAI、抗体亲和力和抗体亲合力分析。结果。来自具有或不具有预先存在免疫力的受试者的人类疫苗接种后血清表现出针对 H3 变体病毒的不同交叉反应性。同样，重复接触 H3 诱导的雪貂交叉反应抗体的范围也扩大了。随着暴露次数的增加，以雪貂抗血清为特征的 H3 病毒之间的抗原差异变得更小。尽管反复暴露于 H3 会导致针对后来暴露的病毒的 HAI 滴度出现“原始抗原原罪”现象，但所得的雪貂抗体显示出对不同 H3/血凝素的亲和力逐渐增强。发现抗体亲和力的增加与所表征的 H3 病毒之间抗原差异的减少呈负相关。结论。我们的结果表明，重复的 H3 暴露不仅会影响抗体的数量，还会影响抗体的质量。目前用于疫苗株选择的“幼稚”雪貂模型并不能概括人类预先存在的免疫力的复杂性。特此鉴定的疫苗株可能无法为那些经常感染和/或接种疫苗的人提供足够的覆盖范围，从而导致观察到的 VE 减少。
Background. Reduced seasonal influenza vaccine effectiveness (VE) was observed in individuals who received repeated annual vaccinations. Preexisting influenza antibody levels were also found inversely correlated with postvaccination titers. These reports suggest that preexisting immunity may affect contemporary seasonal vaccine performance.Methods. Influenza A/H3 specific cross-reactivity of postvaccination sera from humans with or without preexisting immunity was assessed by hemagglutination inhibition (I IAI) assay. Ferret antisera induced by repeated H3 exposures were also subjected to HAI, antibody affinity, and antibody avidity analyses.Results. Human postvaccination sera derived from subjects with or without preexisting immunity showed different cross-reactivity against H3 variant viruses. Similarly, the breadth of cross-reactive ferret antibodies induced by repeated H3 exposures was also broadened. Antigenic differences between H3 viruses characterized by ferret antisera became smaller as the number of exposures increased. Although repeated H3 exposures induced "original antigenic sin" phenomena in HAI titers against later exposed viruses, resultant ferret antibodies showed gradually enhanced avidity for different H3/hemagglutinin. Increased antibody avidity was found to be inversely correlated with decreased antigenic differences among H3 viruses characterized.Conclusions. Our results suggest that repeated H3 exposures imprinted not only antibody quantity but also antibody quality. The "naive" ferret model currently used for vaccine strain selection does not recapitulate the complexity of human preexisting immunity. Vaccine strains identified hereby may not provide coverage sufficient for those who were frequently infected and/or vaccinated, leading to the reduced VE observed.