抗HIV中和抗体的亲和成熟及Tfh细胞的调节作用
Affinity maturation of anti-HIV neutralizing antibodies and regulation of Tfh cells
摘要现在已经明确广谱中和抗体(broad-spectrum neutralizing antibodies,bNAbs)具有抑制人类免疫缺陷病毒(human immunodeficiency virus,HIV)在机体复制和降低血浆中总病毒载量的作用,这也是HIV疫苗设计的主要目标。但是至今传统的疫苗设计策略并不能有效诱导产生bNAbs。通常只有10%~25%慢性HIV感染者才能诱导产生bNAbs。bNAbs具有高频率的体细胞超突变(high frequency of somatic hypermutation)及特有的CDR3区长度等特征,还需要在更有效的滤泡辅助性T细胞(follicular helper T cells)作用下,经历多轮亲和力成熟,才能产生中和能力强、且中和谱较广的中和抗体。因此明确抗HIV中和抗体的亲和成熟特征以及Tfh细胞对其的调节机制是至关重要的,也为设计出能够产生bNAbs的HIV疫苗提供基础。
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abstractsIt has now been established that broad-spectrum neutralizing antibodies(bNAbs) have the effect of inhibiting the replication of human immunodeficiency virus(HIV) in the body and reducing the total viral load in plasma. It also has been the primary targets of HIV vaccine design. However, traditional vaccine design strategies have not been effective in inducing the production of bNAbs. Usually only 10%~25% of chronic HIV-infected individuals can induce bNAbs. bNAbs have high frequency of somatic hypermutation(SHM) and unique CDR3 length. It also needs to undergo multiple rounds of affinity maturation under the action of more effective follicular helper T cells to produce neutralizing antibodies with strong neutralization ability and wide neutralization spectrum. Therefore, it is very important to clarify the affinity maturation characteristics of anti-HIV neutralizing antibodies and the regulatory mechanisms of Tfh cells, which will provide the basis for designing HIV vaccine that can produce bNAb.
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