Immunogenic Stimulus for Germline Precursors of Antibodies that Engage the Influenza Hemagglutinin Receptor-Binding Site.
Immunogenic Stimulus for Germline Precursors of Antibodies that Engage the Influenza Hemagglutinin Receptor-Binding Site.
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DOI：
10.1016/j.celrep.2015.11.063
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发表时间：
2015-12-29
期刊：
影响因子：
8.8
通讯作者：
Harrison SC
中科院分区：
文献类型：
--
作者：
Schmidt AG;Do KT;McCarthy KR;Kepler TB;Liao HX;Moody MA;Haynes BF;Harrison SC
流感病毒抗原性进化以逃避宿主免疫保护。个体内的抗体谱系依次进化以增加亲和力和效力。“通用”流感疫苗的策略，以诱导谱系逃避这种进化军备竞赛，并保护免受季节性变化和新型大流行病毒的影响，将需要指导b细胞的个体发生，将体液反应集中在病毒血凝素（HA）的保守表位上。来自一个个体的六种不同的、广泛中和的抗体谱系的未突变共同祖先（UCAs）与参与者出生时流行的病毒的HA结合。5年后循环的病毒的ha不再结合uca，但谱系中的成熟抗体结合参与者整个18年生命中的菌株。该分析显示了免疫记忆如何形成对随后流感暴露的反应，并表明通过适当的流感抗原早期印记可能会增加后来广度的可能性。
Influenza-virus antigenicity evolves to escape host immune protection. Antibody lineages within individuals evolve in turn to increase affinity and hence potency. Strategies for a “universal” influenza vaccine to elicit lineages that escape this evolutionary arms race and protect against seasonal variation and novel, pandemic viruses will require directing B-cell ontogeny to focus the humoral response on conserved epitopes on the viral hemagglutinin (HA). The unmutated common ancestors (UCAs) of six distinct, broadly-neutralizing antibody lineages from one individual bind the HA of a virus circulating at the time the participant was born. HAs of viruses circulating more than five years later no longer bind the UCAs, but mature antibodies in the lineages bind strains from the entire 18-year lifetime of the participant. The analysis shows how immunological memory shaped the response to subsequent influenza exposures and suggests that early imprinting by a suitable influenza antigen may enhance likelihood of later breadth.