Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts.
Improved HIV-positive infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts.
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DOI：
10.1016/j.xcrm.2021.100254
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发表时间：
2021-04-20
期刊：
影响因子：
--
通讯作者：
Overbaugh J
中科院分区：
文献类型：
--
作者：
Yaffe ZA;Naiman NE;Slyker J;Wines BD;Richardson BA;Hogarth PM;Bosire R;Farquhar C;Ngacha DM;Nduati R;John-Stewart G;Overbaugh J
定义保护人类免受多种艾滋病病毒毒株侵害的免疫反应一直是难以捉摸的。研究母婴传播保护的相关性为艾滋病毒疫苗保护提供了基准，因为婴儿通过母乳接触艾滋病毒期间存在被动转移的艾滋病毒抗体。我们小组之前的一项研究表明，被动获得的抗体依赖性细胞毒性（ADCC）活性与婴儿存活率的提高相关，而中和则不然。在这里，我们在另一个队列中通过两种效应测量表明，被动获得的 ADCC 抗体与婴儿存活率相关。在对两个队列的数据进行综合分析时，较高的婴儿存活率与被动获得的 ADCC 水平 (p = 0.029) 以及二聚体 FcγRIIa (p = 0.002) 或二聚体 FcγRIIIa 结合 (p < 0.001) 之间存在高度统计学上显着的关联。这些结果表明，自然杀伤 (NK) 细胞和单核细胞抗体介导的效应功能可能有助于观察到的生存获益，并支持预先存在的 ADCC 介导抗体在临床结果中的作用。 ADCC 活性与 HIV 感染婴儿的生存率提高有关 与 Fcγ 受体二聚体形式的结合也与生存率有关 这些数据支持 ADCC 在改善感染婴儿的临床结果中的作用 母婴传播是定义 HIV 发病机制保护相关性的独特环境。亚菲等人。研究表明，通过两种测定方法测量的被动获得性 ADCC 与两个母乳喂养队列中感染 HIV 的婴儿生存率的提高相关。这些结果表明，预先存在的 ADCC 介导抗体有助于改善 HIV 阳性婴儿的临床结果。
Defining immune responses that protect humans against diverse HIV strains has been elusive. Studying correlates of protection from mother-to-child transmission provides a benchmark for HIV vaccine protection because passively transferred HIV antibodies are present during infant exposure to HIV through breast milk. A previous study by our group illustrated that passively acquired antibody-dependent cellular cytotoxicity (ADCC) activity is associated with improved infant survival whereas neutralization is not. Here, we show, in another cohort and with two effector measures, that passively acquired ADCC antibodies correlate with infant survival. In combined analyses of data from both cohorts, there are highly statistically significant associations between higher infant survival and passively acquired ADCC levels (p = 0.029) as well as dimeric FcγRIIa (p = 0.002) or dimeric FcγRIIIa binding (p < 0.001). These results suggest that natural killer (NK) cell- and monocyte antibody-mediated effector functions may contribute to the observed survival benefit and support a role of pre-existing ADCC-mediating antibodies in clinical outcome. ADCC activity is associated with improved survival of HIV-infected infants Binding to dimeric forms of Fcγ receptors is also associated with survival These data support a role of ADCC in improved clinical outcome in infected infants Mother-to-child transmission is a unique setting to define correlates of protection from HIV pathogenesis. Yaffe et al. show that passively acquired ADCC, measured by two assays, correlates with improved survival of HIV-infected infants in two breastfeeding cohorts. These results suggest that pre-existing, ADCC-mediating antibodies contribute to improved HIV-positive infant clinical outcome.
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影响因子：
6.4
作者：
LJUNGGREN, K;MOSCHESE, V;JONDAL, M
通讯作者：
JONDAL, M
影响因子：
29.7
作者：
Bournazos S;Wang TT;Dahan R;Maamary J;Ravetch JV
通讯作者：
Ravetch JV
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH
影响因子：
2.2
作者：
Gómez-Román, VR;Florese, RH;Robert-Guroff, M
通讯作者：
Robert-Guroff, M
影响因子：
3.8
作者：
Madhavi, Vijaya;Wren, Leia H.;Stratov, Ivan
通讯作者：
Stratov, Ivan