Immunogenicity of the outer domain of a HIV-1 clade C gp120.
Immunogenicity of the outer domain of a HIV-1 clade C gp120.
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DOI：
10.1186/1742-4690-4-33
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发表时间：
2007-05-17
期刊：
影响因子：
3.3
通讯作者：
Jones, Ian M.
中科院分区：
文献类型：
--
作者：
Chen, Hongying;Xu, Xiaodong;Jones, Ian M.
研究了 C 进化枝 HIV-1 gp120 的子结构域可以充当有效免疫原的可能性。为此，在由重新引入的 MAb 2G12 构象表位标记的构建体中表达和表征了 gp120CN54 的外部结构域 (OD)。表达的序列在分离的 ODCN54 上显示出有效的表位保留，表明真实的折叠。为了促进纯化和随后的免疫原性，ODCN54 与人 IgG1 的 Fc 结构域融合。用所得融合蛋白以及单独的gp120CN54-Fc和gp120对小鼠进行免疫。发现与 Fc 的融合可刺激抗体滴度，并且 Fc 标记的 ODCN54 比未标记的 gp120 具有显着更高的免疫原性。免疫原性似乎是 Fc 促进抗原加工的结果，因为用 Fc 结构域突变体进行免疫，与亲本序列相比，减少与 FcR 的结合导致抗体滴度降低。通过与细菌中表达为 GST 融合蛋白的 gp120CN54 的五个重叠片段的血清反应来评估抗体反应的广度。用gp120CN54-Fc免疫后观察到主要的抗内部结构域和抗V3C3反应以及对ODCN54-Fc融合的抗V3C3反应。 gp120CN54 的外部结构域在表达为 C 末端融合蛋白后正确折叠。当靶向抗原呈递细胞时，免疫原性是显着的，但在多价反应中显示出 V3 的优势。 gp120 外部结构域具有作为候选疫苗成分的潜力。
The possibility that a sub domain of a C clade HIV-1 gp120 could act as an effective immunogen was investigated. To do this, the outer domain (OD) of gp120CN54 was expressed and characterized in a construct marked by a re-introduced conformational epitope for MAb 2G12. The expressed sequence showed efficient epitope retention on the isolated ODCN54 suggesting authentic folding. To facilitate purification and subsequent immunogenicity ODCN54 was fused to the Fc domain of human IgG1. Mice were immunised with the resulting fusion proteins and also with gp120CN54-Fc and gp120 alone. Fusion to Fc was found to stimulate antibody titre and Fc tagged ODCN54 was substantially more immunogenic than non-tagged gp120. Immunogenicity appeared the result of Fc facilitated antigen processing as immunisation with an Fc domain mutant that reduced binding to the FcR lead to a reduction in antibody titre when compared to the parental sequence. The breadth of the antibody response was assessed by serum reaction with five overlapping fragments of gp120CN54 expressed as GST fusion proteins in bacteria. A predominant anti-inner domain and anti-V3C3 response was observed following immunisation with gp120CN54-Fc and an anti-V3C3 response to the ODCN54-Fc fusion. The outer domain of gp120CN54 is correctly folded following expression as a C terminal fusion protein. Immunogenicity is substantial when targeted to antigen presenting cells but shows V3 dominance in the polyvalent response. The gp120 outer domain has potential as a candidate vaccine component.
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DOI：
10.1084/jem.173.6.1483
发表时间：
1991-06-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Canfield SM;Morrison SL
通讯作者：
Morrison SL
影响因子：
4.1
作者：
Chapple, SDJ;Jones, IM
通讯作者：
Jones, IM
影响因子：
3.7
作者：
Kothe, Denise L.;Li, Yingying;Hahn, Beatrice H.
通讯作者：
Hahn, Beatrice H.
影响因子：
5.4
作者：
Balzarini, J;Van Laethem, K;Schols, D
通讯作者：
Schols, D
影响因子：
3.6
作者：
Balzarini, J;Van Laethem, K;Schols, D
通讯作者：
Schols, D