Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity: relevance to global HIV vaccine design
Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity: relevance to global HIV vaccine design
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DOI：
10.1097/qad.0000000000000310
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发表时间：
2014-08-24
期刊：
影响因子：
3.8
通讯作者：
Stratov, Ivan
中科院分区：
文献类型：
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作者：
Madhavi, Vijaya;Wren, Leia H.;Stratov, Ivan
目的：研究HIV控制者和HIV进展者对HIV-1环境特异性抗体依赖的细胞毒作用(ADCC)的广度，以期设计具有全球相关性的HIV疫苗。设计：体外测定11名HIV控制者和11名HIV进展者对4种主要HIV-1环境亚型的ADCC广度。方法：分析11名HIV控制者(包括长期慢进者、病毒控制者、精英控制者和治疗后控制者)和11名HIV进展者(主要感染HIV-1 B亚型)的ADCC反应。结果：人类免疫缺陷病毒控制组的自然杀伤细胞激活范围明显大于进展组(P=0.02)，其激活幅度也高于进展组(P<0.001)。与HIV-1B亚型和异源E亚型gp140的HIV进展者相比，HIV控制者对包膜包膜的靶细胞的杀伤率也显著高于HIV-1gp140(P=0.001)。我们发现ADCC对B和E亚型envs具有良好的反应性，与A亚型的交叉反应性较低，与C亚型env的交叉反应性最小。糖基化依赖的adcc表位在整个环境特异性adcc反应中占很大比例，从adcc减少到非糖化形式的HIV-1gp140(P=0.004)可以明显看出这一点。研究发现，Env的糖基化对于识别ADCC表位是重要的。识别保守的ADCC表位将有助于设计全球相关的基于ADCC的艾滋病毒疫苗。(C)2014沃尔特斯·克鲁沃健康|Lippincott Williams&Wilkins
Objective: The objective of this study is to determine the breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity (ADCC) in HIV controllers and HIV progressors with a view to design globally relevant HIV vaccines.Design: The breadth of ADCC towards four major HIV-1 Env subtypes was measured in vitro for 11 HIV controllers and 11 HIV progressors.Methods: Plasma from 11 HIV controllers (including long-term slow progressors, viremic controllers, elite controller and posttreatment controller) and 11 HIV progressors, mostly infected with HIV-1 subtype B, was analysed for ADCC responses. ADCC assays were performed against 10 HIV-1 gp120 and 8 gp140 proteins from four major HIV-1 subtypes (A, B, C and E) and 3 glycosylation-mutant gp140 proteins.Results: ADCC-mediated natural killer cell activation was significantly broader (P = 0.02) and of higher magnitude (P < 0.001) in HIV controllers than in HIV progressors. HIV controllers also showed significantly higher magnitude of ADCC-mediated killing of Env-coated target cells than HIV progressors to both HIV-1 subtype B and the heterologous subtype E gp140 (P = 0.001). We found good ADCC reactivity to subtype B and E Envs, less cross-reactivity to subtype A and minimal cross-reactivity to subtype C Envs. Glycosylation-dependent ADCC epitopes comprise a significant proportion of the total Env-specific ADCC response, as evident from the reduction in ADCC to nonglycosylated form of HIV-1 gp140 (P = 0.004).Conclusion: HIV controllers have robust ADCC responses that recognize a broad range of HIV-1 Env. Glycosylation of Env was found to be important for recognition of ADCC epitopes. Identifying conserved ADCC epitopes will assist in designing globally relevant ADCC-based HIV vaccines. (C) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins