Impact of HIV-1 backbone on neutralization sensitivity: neutralization profiles of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE backbone.
Impact of HIV-1 backbone on neutralization sensitivity: neutralization profiles of heterologous envelope glycoproteins expressed in native subtype C and CRF01_AE backbone.
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DOI：
10.1371/journal.pone.0076104
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tovanabutra S
中科院分区：
文献类型：
--
作者：
Chenine AL;Wieczorek L;Sanders-Buell E;Wesberry M;Towle T;Pillis DM;Molnar S;McLinden R;Edmonds T;Hirsch I;O'Connell R;McCutchan FE;Montefiori DC;Ochsenbauer C;Kappes JC;Kim JH;Polonis VR;Tovanabutra S
评估疫苗和抗病毒药物有效性的标准化检测对于开发保护性HIV-1疫苗和药物至关重要。这些免疫测定将通过开发标准化的病毒原种（例如HIV-1感染性分子克隆（IMC））来推进，所述标准化的病毒原种i）表达报告基因，ii）代表全球不同的亚型，和iii）被工程化以容易地交换包膜（env）基因以表达感兴趣的序列。到目前为止，已经成功开发了表达海肾荧光素酶（LucR）的B亚型IMC骨架，并且异源env编码序列的胞外域可以表达到该骨架中，但是随着HIV-1疫苗效力试验的执行越来越多地转移到非亚型B流行病（南部非洲和东南亚），需要非亚型B HIV-1试剂来支持疫苗开发。在这里，我们描述了两个IMC来自亚型C和CRF01_AE HIV-1表达LucR的主要分离株（IMC.LucR），它们被工程化以表达异源gp 160 Envs。测试了在亚型匹配和不匹配的HIV主链中表达各种亚型C和CRF01_AE Env（大多数是急性的）的18种构建体的功能性和中和敏感性。我们的研究结果表明，非env HIV-1基因对Env和中和抗体相互作用的可能影响，并强调需要产生一个代表HIV-1亚型谱的IMC库，用作评估HIV-1疫苗效力的标准化中和试验试剂。
Standardized assays to assess vaccine and antiviral drug efficacy are critical for the development of protective HIV-1 vaccines and drugs. These immune assays will be advanced by the development of standardized viral stocks, such as HIV-1 infectious molecular clones (IMC), that i) express a reporter gene, ii) are representative of globally diverse subtypes and iii) are engineered to easily exchange envelope (env) genes for expression of sequences of interest. Thus far, a subtype B IMC backbone expressing Renilla luciferase (LucR), and into which the ectodomain of heterologous env coding sequences can be expressed has been successfully developed but as execution of HIV-1 vaccine efficacy trials shifts increasingly to non-subtype B epidemics (Southern African and Southeast Asia), non-subtype B HIV-1 reagents are needed to support vaccine development. Here we describe two IMCs derived from subtypes C and CRF01_AE HIV-1 primary isolates expressing LucR (IMC.LucR) that were engineered to express heterologous gp160 Envs. 18 constructs expressing various subtypes C and CRF01_AE Envs, mostly acute, in subtype-matched and –unmatched HIV backbones were tested for functionality and neutralization sensitivity. Our results suggest a possible effect of non-env HIV-1 genes on the interaction of Env and neutralizing antibodies and highlight the need to generate a library of IMCs representative of the HIV-1 subtype spectrum to be used as standardized neutralization assay reagents for assessing HIV-1 vaccine efficacy.
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影响因子：
3.7
作者：
Edmonds TG;Ding H;Yuan X;Wei Q;Smith KS;Conway JA;Wieczorek L;Brown B;Polonis V;West JT;Montefiori DC;Kappes JC;Ochsenbauer C
通讯作者：
Ochsenbauer C
DOI：
10.1093/infdis/jis367
发表时间：
2012-08-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Montefiori DC;Karnasuta C;Huang Y;Ahmed H;Gilbert P;de Souza MS;McLinden R;Tovanabutra S;Laurence-Chenine A;Sanders-Buell E;Moody MA;Bonsignori M;Ochsenbauer C;Kappes J;Tang H;Greene K;Gao H;LaBranche CC;Andrews C;Polonis VR;Rerks-Ngarm S;Pitisuttithum P;Nitayaphan S;Kaewkungwal J;Self SG;Berman PW;Francis D;Sinangil F;Lee C;Tartaglia J;Robb ML;Haynes BF;Michael NL;Kim JH
通讯作者：
Kim JH
影响因子：
3.8
作者：
Cheung, L;McLain, L;Dimmock, NJ
通讯作者：
Dimmock, NJ
影响因子：
5.4
作者：
Kalia, V;Sarkar, S;Montelaro, RC
通讯作者：
Montelaro, RC
影响因子：
3.8
作者：
Matyas, Gary R.;Wieczorek, Lindsay;Alving, Carl R.
通讯作者：
Alving, Carl R.