Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 Vaccination.
Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 Vaccination.
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DOI：
10.3389/fimmu.2017.01883
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发表时间：
2017
影响因子：
7.3
通讯作者：
Shattock RJ
中科院分区：
文献类型：
--
作者：
Kratochvil S;McKay PF;Chung AW;Kent SJ;Gilmour J;Shattock RJ
抗体亚类表现出广泛的多态性（同种异型），可能会影响HIV疫苗诱导的B细胞应答的质量。同种异型免疫球蛋白（IG）G1，最丰富的血清抗体，已被证明显示改变的功能特性，血清半衰期，Fc受体结合和FcRn介导的粘膜转胞吞。为了研究同种异型IgG 1变异体和疫苗产生的体液应答之间的潜在联系，在14名HIV疫苗接种者的队列中，我们开发了一种新的快速IgG 1同种异型分型方案。我们结合PCR和ELISA检测，采用双重方法，使用人血浆和从PBMC中分离的RNA，确定试验参与者的IgG 1同种异型身份（G1 m3和/或G1 m1）。我们的参与者的IgG 1同种异型分布反映了先前报道的高加索人群的结果。我们观察到HIV gp 140特异性IgG 1水平升高，与G1 m1等位基因相关的IgG 2水平降低，与G1 m3携带者相反。这些数据表明，与G1 m3携带者相比，G1 m1纯合子疫苗接种者更易发生Ag特异性IgG 1：IgG 2比值升高。这种IgG 1：IgG 2比值升高进一步与Fcγ R-二聚体结合率升高相关，Fc γ R-二聚体结合率是潜在抗体依赖性细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP）功能的替代指标。虽然是初步的，这些结果表明，IgG 1同种异型可能有一个显着的影响IgG亚类的分布在响应疫苗接种和相关的Fc介导的效应功能。这些结果对正在进行的HIV疫苗有效性研究具有重要意义，这些研究基于Fcγ R介导的细胞功能（包括ADCC和ADCP）的参与，需要进一步研究。我们的新型同种异型分型方案提供了新的工具来确定IgG 1同种异型对疫苗效力的潜在影响。
Antibody subclasses exhibit extensive polymorphisms (allotypes) that could potentially impact the quality of HIV-vaccine induced B cell responses. Allotypes of immunoglobulin (Ig) G1, the most abundant serum antibody, have been shown to display altered functional properties in regard to serum half-life, Fc-receptor binding and FcRn-mediated mucosal transcytosis. To investigate the potential link between allotypic IgG1-variants and vaccine-generated humoral responses in a cohort of 14 HIV vaccine recipients, we developed a novel protocol for rapid IgG1-allotyping. We combined PCR and ELISA assays in a dual approach to determine the IgG1 allotype identity (G1m3 and/or G1m1) of trial participants, using human plasma and RNA isolated from PBMC. The IgG1-allotype distribution of our participants mirrored previously reported results for caucasoid populations. We observed elevated levels of HIV gp140-specific IgG1 and decreased IgG2 levels associated with the G1m1-allele, in contrast to G1m3 carriers. These data suggest that vaccinees homozygous for G1m1 are predisposed to develop elevated Ag-specific IgG1:IgG2 ratios compared to G1m3-carriers. This elevated IgG1:IgG2 ratio was further associated with higher FcγR-dimer engagement, a surrogate for potential antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) function. Although preliminary, these results suggest that IgG1 allotype may have a significant impact on IgG subclass distribution in response to vaccination and associated Fc-mediated effector functions. These results have important implications for ongoing HIV vaccine efficacy studies predicated on engagement of FcγR-mediated cellular functions including ADCC and ADCP, and warrant further investigation. Our novel allotyping protocol provides new tools to determine the potential impact of IgG1 allotypes on vaccine efficacy.
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DOI：
10.1007/978-1-61779-842-9_34
发表时间：
2012-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Lefranc, Marie-Paule;Lefranc, Gerard
通讯作者：
Lefranc, Gerard
影响因子：
2.6
作者：
Magdelaine-Beuzelin, Charlotte;Vermeire, Severine;Watier, Herve
通讯作者：
Watier, Herve
影响因子：
3.7
作者：
OXELIUS, VA
通讯作者：
OXELIUS, VA
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
影响因子：
7.3
作者：
Joseph S;Quinn K;Greenwood A;Cope AV;McKay PF;Hayes PJ;Kopycinski JT;Gilmour J;Miller AN;Geldmacher C;Nadai Y;Ahmed MI;Montefiori DC;Dally L;Bouliotis G;Lewis DJ;Tatoud R;Wagner R;Esteban M;Shattock RJ;McCormack S;Weber J
通讯作者：
Weber J