人类免疫缺陷病毒1型的广谱中和抗体的亲和力成熟与特征及其运用  

The affinity maturation,characteristics and application of HIV-1 broadly neutralizing antibodies

作　　者：万鑫蕊 孙明[2] 李娅[1] Wan Xinrui;Sun Ming;Li Ya(Department of Clinical Laboratory,the First Affiliated Hospital of Kunming Medical University,Yunnan Key Laboratory of Laboratory Medicine,Yunnan Innovation Team of Diagnosis,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China;Institute of Medical Biology,Chinese Academy of Medical Science and Peking Union Medical College,Kunming 650118,China)

机构地区：[1]昆明医科大学第一附属医院医学检验科云南省检验医学重点实验室昆明医科大学第一附属医院临床检验诊断省创新团队,昆明650032 [2]中国医学科学院北京协和医学院医学生物学研究所,昆明650118

出　　处：《中华预防医学杂志》2022年第2期225-232,共8页Chinese Journal of Preventive Medicine

基　　金：云南省教育厅科学研究基金(2020J0171);云南省临床检验诊断创新团队(202005AE160009);云南省卫生健康委员会医学学科带头人培养计划(D-2018025,D-2019022)。

摘　　要：人类免疫缺陷病毒1型(HIV-1)感染的长期不进展者(LTNP)体内分离到的广谱中和抗体(bNAbs),已被证明可以预防HIV-1感染并降低感染者体内的病毒载量,成为了指导HIV-1疫苗设计和被动免疫治疗的突破口。中和抗体的功能除了与靶向表位有关,其亲和力也极大的影响了抗体的活性。HIV-1 bNAbs通过体内的多轮亲和力成熟获得了较高亲和力,从而实现了广谱度和中和活性的增加。高亲和力HIV-1 bNAbs在治疗过程中能更好的协助机体免疫系统清除病原体,并且使用剂量更少,毒副作用也相对较低。在亲和力成熟的同时,HIV-1 bNAbs表现出了高水平的体细胞超突变(SHM)、插入缺失、较长的重链第三互补决定区等不寻常的特征。这些特征阻碍了通过有效疫苗诱导HIV-1 bNAbs在体内产生并发育成熟,因此了解抗体亲和力成熟过程中发生的突变及其要点,有助于理解中和抗体的活性与特征的关系,并为设计有效的HIV-1潜在免疫原提供参考。Hundreds of broadly neutralizing antibodies(bNAbs)were successfully isolated from long-term nonprogression(LTNP)of human immunodeficiency virus type 1(HIV-1)infected individuals.Some bNAbs were illustrated could reduce the viral load and the risk of HIV-1 infection.Today,HIV-1 bNAbs are at the center of vaccine development and passive immunization treatment.Usually,the activity of neutralizing antibodies depends on the epitope.The affinity of neutralizing antibodies also plays a vital role in its inhibitory effect.Multiple affinity maturation in vivo actually provides the broad and potent neutralizing activity of HIV-1 bNAbs.When high affinity HIV-1 bNAbs applied in clinic,it can help immune system to remove virus with lower dosage and fewer side effect.While affinity maturation,HIV-1 bNAbs shows unique characteristics,such as extensive of somatic hypermutation(SHM),in-frame insertion and deletion and long CDR 3 region of heavy chain.The key points in the progress that HIV-1 bNAbs affinity maturation will help us understand the relationship between antibodies neutralizing capability and its characteristics.It also potentially provide a reference to design effective HIV-1 immunogen.

关 键 词：人类免疫缺陷病毒 广谱中和抗体 抗体亲和力 疫苗 

分 类 号：R392-33[医药卫生—免疫学]