Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity.

Pre-existing infant antibody-dependent cellular cytotoxicity associates with reduced HIV-1 acquisition and lower morbidity.
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预先存在的婴儿抗体依赖的细胞毒性与HIV-1感染减少和发病率降低有关。

DOI:
10.1016/j.xcrm.2021.100412
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发表时间:
2021-10-19
期刊:
Cell reports. Medicine
影响因子:
--
通讯作者:
Sagar M
Sagar M
中科院分区:
其他
文献类型:
--
作者:
Thomas AS;Moreau Y;Jiang W;Isaac JE;Ewing A;White LF;Kourtis AP;Sagar M

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在人类中,预先存在的抗HIV-1中和抗体(nAb)与HIV-1感染减少无关。在这里,我们评估抗体依赖性细胞毒性(ADCC)存在于传播前的婴儿和母亲的血浆和母乳(BM)对同期产妇HIV-1变异。与HIV-1暴露的感染婴儿相比,HIV-1暴露的未感染婴儿具有更高的ADCC以及ADCC和针对其相应母亲菌株的nAb应答的组合。ADCC与nAb不相关,表明它们是独立的活动。与低ADCC相比,具有高ADCC的感染婴儿在出生后1年内的发病率较低,但不包括具有较高ADCC加nAb的感染婴儿。在BM上清液中观察到较高的IgA与IgG比率,并且与未感染的婴儿相比,在较高比例的感染中观察到较高的IgA与IgG比率,与较低的ADCC相关。相对于暴露菌株,ADCC比nAbs更能降低母婴传播和感染后婴儿发病率。具有较高ADCC的婴儿对他们母亲的菌株获得艾滋病毒的频率较低感染的婴儿具有较高的传播前ADCC反应有更好的结果ADCC活性与中和抗体反应无关高伊加水平与较低的ADCC活性相关托马斯等人。表明对暴露菌株的更高的预先存在的ADCC应答与HIV-1母婴传播的可能性较小和受感染婴儿的发病率较低相关。
In humans, pre-existing anti-HIV-1 neutralizing antibodies (nAbs) have not been associated with decreased HIV-1 acquisition. Here, we evaluate antibody-dependent cellular cytotoxicity (ADCC) present in pre-transmission infant and maternal plasma and breast milk (BM) against the contemporaneous maternal HIV-1 variants. HIV-1-exposed uninfected compared with HIV-1-exposed infected infants have higher ADCC and a combination of ADCC and nAb responses against their corresponding mother’s strains. ADCC does not correlate with nAbs, suggesting they are independent activities. The infected infants with high ADCC compared with low ADCC, but not those with higher ADCC plus nAbs, have lower morbidity up to 1 year after birth. A higher IgA to IgG ratio, observed in BM supernatants and in a higher proportion of the infected compared with the uninfected infants, associates with lower ADCC. Against the exposure strains, ADCC, more than nAbs, associates with both lower mother-to-child transmission and decreased post-infection infant morbidity. Infants with higher ADCC against their mother’s strains acquire HIV less frequently Infected infants with higher pre-transmission ADCC responses have better outcomes ADCC activity does not correlate with neutralizing antibody responses High IgA levels associate with lower ADCC activity Thomas et al. show that higher pre-existing ADCC responses against exposure strains associate with less likelihood of HIV-1 mother-to-child transmission and lower morbidity in infected infants.
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