Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
Clin Infect Dis. 2017 Jul 15;65(2):259-267. doi: 10.1093/cid/cix269.
Effectiveness of seasonal influenza vaccines mainly depends upon how well vaccine strains represent circulating viruses; mismatched strains can lead to reduced protection. Humans have complex influenza exposure histories that increase with age, which may lead to different postvaccination responses to emerging influenza variants. Recent observational studies also suggest that prior vaccination may influence the performance of current seasonal vaccines.
To elucidate the effects of age and influenza preexposures on cross-reactivity of vaccination-induced human antibodies, we generated antigenic maps based on postvaccination hemagglutination inhibition titers against representative H3 variants circulating during the 2015-2016, 2014-2015, and 2012-2013 influenza seasons.
Antigenic maps determined using sera from subjects 18-64 and ≥65 years of age correlated well with each other but poorly with those determined using sera from children. Antigenic maps derived from human postvaccination sera with H1 influenza preexposure also correlated poorly with those derived from sera with neither H1 nor type B influenza preexposure, and the correlation lessened considerably over time. In contrast, antigenic maps derived from human postvaccination sera with only type B influenza preexposure consistently showed good correlation with those derived from sera with neither H1 nor type B influenza preexposure.
Our results suggest an age-specific difference in human postvaccination responses. Our findings also suggest that prior exposure to H1 or type B influenza may differentially affect cross-reactivity of vaccination-induced H3-specific hemagglutination inhibition antibody responses, and consequently might affect vaccine effectiveness. Our study highlights the need to study the impact of prior exposure on influenza vaccine performance.
季节性流感疫苗的有效性主要取决于疫苗株对流行病毒的代表性如何；不匹配的毒株可能导致保护效果降低。人类有复杂的流感接触史，随着年龄的增长而增加，这可能导致对新出现的流感变异体产生不同的接种后反应。最近的观察性研究还表明，先前的接种可能会影响当前季节性疫苗的效果。
为了阐明年龄和流感预先暴露对接种诱导的人类抗体交叉反应性的影响，我们根据 2015-2016、2014-2015 和 2012-2013 流感季节流行的代表性 H3 变体的接种后血凝抑制滴度生成了抗原图谱。
使用 18-64 岁和≥65 岁受试者的血清确定的抗原图谱彼此相关性良好，但与儿童血清的相关性较差。使用具有 H1 流感预先暴露的人类接种后血清确定的抗原图谱与既没有 H1 也没有 B 型流感预先暴露的血清确定的抗原图谱也相关性较差，并且随着时间的推移相关性大大减弱。相比之下，仅具有 B 型流感预先暴露的人类接种后血清确定的抗原图谱始终与既没有 H1 也没有 B 型流感预先暴露的血清确定的抗原图谱具有良好的相关性。
我们的结果表明人类接种后反应存在年龄特异性差异。我们的研究结果还表明，先前暴露于 H1 或 B 型流感可能会对接种诱导的 H3 特异性血凝抑制抗体反应的交叉反应性产生不同的影响，从而可能影响疫苗的效果。我们的研究强调了需要研究先前暴露对流感疫苗效果的影响。
