Understanding the impact of imprinted serum antibody repertoire on subsequent vaccine responses

对多种传染病的保护与特定病原体的数量和质量相关 B细胞分泌的抗体(Ab)分子。季节性流感疫苗含有血凝素(HA)蛋白 旨在诱导抗HA抗体，能够对流感感染产生保护性免疫，但 目前的年度流感疫苗只对大约60%的人口提供保护。最近的研究集中在 设计新的基于HA的免疫原，可诱导具有广泛保护性的抗体(BpAbs) 针对不同的流感病毒株，但这些策略引发的bpAbb往往是短暂的。我们之间的差距 关于流感抗体的分子特征、功能和寿命的知识，特别是与 对先前暴露的先前存在的体液记忆的影响，阻碍了能够 产生持久的bpAbs。由于流感的无处不在的性质和建议的季节性 接种疫苗，大多数人在年轻时就接触到流感，许多研究已经做出了 观察表明，儿时接触产生的抗体谱系在免疫系统中留下了印记 并通过随后暴露于漂浮的菌株而持续在循环中。尽管有这些观察， 印迹血清抗体谱的临床相关性及其对后续疫苗的影响的信息 目前还缺乏回应。在这里，我们建议将尖端的转录和蛋白质组学工具应用于Match 用疫苗接种前后的样本区分印迹流感抗体谱系和新诱导的(De) Novo)Abs，以确定印迹Abs的生物物理和功能特征。确定各种途径以实现 克服印迹抗体谱系施加的潜在限制可能是设计一种 通用流感疫苗，可以对不同的流感毒株提供长期保护。

Protection against numerous infectious diseases correlates with the quantity and quality of pathogen-specific antibody (Ab) molecules secreted by B cells. Seasonal flu vaccines contain hemagglutinin (HA) proteins designed to elicit anti-HA Abs capable of conferring protective immunity against influenza infection, but the current annual flu vaccines confer protection only in ~60% of the population. Recent studies have focused on designing new HA-based immunogens that can elicit broadly-protective Abs (bpAbs) capable of protecting against diverse influenza strains, but bpAbs elicited by these strategies are often short-lived. A gap in our knowledge regarding the molecular features, functionalities, and longevity of influenza Abs, specifically related to the impact of pre-existing humoral memory from prior exposure, impedes the design of vaccines capable of generating long-lasting bpAbs. Due to the ubiquitous nature of influenza and recommended seasonal vaccinations, most of the population is exposed to influenza at a young age, and many studies have made observations that suggest Ab repertoire generated from the childhood exposure is ‘imprinted’ in the immune system and persists in circulation through ensuing exposures to drifted strains. Despite these observations, information on the clinical relevance and impact of imprinted serum Ab repertoire on subsequent vaccine responses is lacking. Here, we propose to apply cutting edge transcriptomic and proteomic tools to matched pre- and post-vaccination samples to distinguish the imprinted influenza Ab repertoire from newly elicited (de novo) Abs to define the biophysical and functional features of imprinted Abs. Identifying various avenues for overcoming potential restrictions imposed by the imprinted Ab repertoire could be key for the design of a universal flu vaccine that can confer long-lasting protection against diverse influenza strains.