Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother.
Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother.
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DOI：
10.1016/j.isci.2023.106762
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发表时间：
2023-05-19
期刊：
影响因子：
5.8
通讯作者：
Overbaugh, Julie
中科院分区：
文献类型：
--
作者：
Yaffe, Zak A.;Ding, Shilei;Sung, Kevin;Chohan, Vrasha;Marchitto, Lorie;Doepker, Laura;Ralph, Duncan;Nduati, Ruth;Matsen, Frederick A.;Finzi, Andres;Overbaugh, Julie
人类自然史和疫苗研究支持抗体依赖性细胞毒性（ADCC）活性对许多感染性疾病的保护作用。一直观察到这一点的一种情况是在HIV-1垂直传播中，HIV暴露婴儿被动获得ADCC活性与HIV+婴儿获得风险降低和发病率降低相关。然而，构成母体血浆ADCC应答的HIV特异性抗体的特征还不清楚。在这里，我们从母亲MG 540妊娠晚期的记忆B细胞中重建了单克隆抗体（mAb），尽管有几个高危因素，但她没有将HIV传播给她的婴儿。构建了代表14个克隆家族的20株单克隆抗体，它们介导ADCC并识别多个HIV包膜表位。在使用Fc缺陷型变体的实验中，仅几种mAb的组合占MG 540及其婴儿的大部分血浆ADCC。我们提出这些单克隆抗体作为证据的多克隆剧目与有效的艾滋病毒导向的ADCC活性。ADCC介导的抗体分离自HIV感染的非传播性母亲。多种抗体促成了该个体的血浆ADCC。母亲和早期婴儿血浆中的ADCC抗体库相似。这些发现表明，该母亲的血浆ADCC是由于多克隆应答。
Human natural history and vaccine studies support a protective role of antibody dependent cellular cytotoxicity (ADCC) activity against many infectious diseases. One setting where this has consistently been observed is in HIV-1 vertical transmission, where passively acquired ADCC activity in HIV-exposed infants has correlated with reduced acquisition risk and reduced pathogenesis in HIV+ infants. However, the characteristics of HIV-specific antibodies comprising a maternal plasma ADCC response are not well understood. Here, we reconstructed monoclonal antibodies (mAbs) from memory B cells from late pregnancy in mother MG540, who did not transmit HIV to her infant despite several high-risk factors. Twenty mAbs representing 14 clonal families were reconstructed, which mediated ADCC and recognized multiple HIV Envelope epitopes. In experiments using Fc-defective variants, only combinations of several mAbs accounted for the majority of plasma ADCC of MG540 and her infant. We present these mAbs as evidence of a polyclonal repertoire with potent HIV-directed ADCC activity. ADCC-mediating antibodies were isolated from an HIV-infected non-transmitting mother Multiple antibodies contributed to the plasma ADCC of this individual The ADCC antibody repertoire in maternal and early infant plasma is similar These findings suggest plasma ADCC in this mother is because of a polyclonal response Immunology; Pediatrics; Virology
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影响因子：
7.7
作者：
Garrett ME;Galloway JG;Wolf C;Logue JK;Franko N;Chu HY;Matsen FA 4th;Overbaugh JM
通讯作者：
Overbaugh JM
影响因子：
5.4
作者：
Doepker, Laura E.;Simonich, Cassandra A.;Overbaugh, Julie M.
通讯作者：
Overbaugh, Julie M.
DOI：
10.1073/pnas.1217609110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Guan, Yongjun;Pazgier, Marzena;Lewis, George K.
通讯作者：
Lewis, George K.
影响因子：
5.4
作者：
Earl, PL;Broder, CC;Moss, B
通讯作者：
Moss, B
HIV-1 抗体中抗体依赖性细胞毒性功能的开发。
影响因子：
7.7
作者：
Doepker LE;Danon S;Harkins E;Ralph DK;Yaffe Z;Garrett ME;Dhar A;Wagner C;Stumpf MM;Arenz D;Williams JA;Jaoko W;Mandaliya K;Lee KK;Matsen FA 4th;Overbaugh JM
通讯作者：
Overbaugh JM