Influenza-infected newborn and adult monkeys exhibit a strong primary antibody response to hemagglutinin stem

Influenza-infected newborn and adult monkeys exhibit a strong primary antibody response to hemagglutinin stem
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DOI:
10.1172/jci.insight.135449
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发表时间:
2020-03-12
期刊:
影响因子:
8
通讯作者:
Alexander-Miller, Martha A.
Alexander-Miller, Martha A.
中科院分区:
医学1区
文献类型:
--
作者:
Clemens, Elene;Angeletti, Davide;Alexander-Miller, Martha A.

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针对甲型流感病毒(IAV)感染产生的抗体(Abs)的特异性可以显著改变病毒的保护和清除。目前,年龄对这一过程的影响还相对较少。在这里,我们评估了新生和成年非洲绿猴感染IAV后的抗体反应,使用一种菌株,使用户能够确定血凝素(HA)抗体反应的免疫优势(ID)等级,HA是保护性抗体的主要目标。这揭示了新生儿与成年人早期IgM抗HA反应中ID模式的变化,这种模式随着时间的推移而收敛。虽然新生猴子和成年猴子的HA免疫球蛋白ID分布相似,但IgA并非如此。重要的是,HA干细胞特异性抗体在新生儿和成人中生成旺盛,在质量和数量上都是相似的。总之,这些结果表明,新生儿和成人在感染后建立的抗体ID模式可能不同,并且ID模式可能因同种类型而不同。此外,新生儿有能力产生强大的HA干细胞特异性抗体反应。我们的发现进一步了解了新生儿对IAV抗原的反应,并为为这一高危人群开发改进的疫苗提供了信息。
The specificity of antibodies (Abs) generated against influenza A virus (IAV) infection can significantly alter protection and viral clearance. At present, the impact of age upon this process is relatively unexplored. Here, we evaluated the Ab response in newborn and adult African green monkeys following infection with IAV using a strain that enables usto determine the immunodominance (ID) hierarchy of the Ab response to hemagglutinin (HA), the principal target of protective Abs. This revealed altered ID patterns in the early IgM anti-HA response in newborns versus adults that converged over time. While the lgG ID profiles for HA in newborn and adult monkeys were similar, this was not the case for IgA. Importantly, HA stem-specific Abs were generated robustly and similarly in newborns and adults in terms of quality and quantity. Together, these results demonstrate that newborns and adults can differ in the Ab ID pattern established following infection and that the ID pattern can vary across isotypes. In addition, newborns have the ability to generate potent HA stem-specific Ab responses. Our findings further the understanding of the newborn response to IAV antigens and inform the development of improved vaccines for this at-risk population.