Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins
Factors limiting the immunogenicity of HIV-1 gp120 envelope glycoproteins
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DOI：
10.1016/j.virol.2004.08.037
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发表时间：
2004-12-05
期刊：
影响因子：
3.7
通讯作者：
Wyatt, R
中科院分区：
文献类型：
--
作者：
Grundner, C;Pancera, M;Wyatt, R
对HIV-1基因产物的有效免疫反应是开发和设计有效疫苗的基本要素。理想情况下，体液反应和细胞反应都能以最佳方式激发。因此，阐明可能限制有效疫苗中可能包括的HIV-1蛋白免疫原性的任何因素都是重要的。由于HIV-1外膜糖蛋白gp120是中和抗体的主要靶点，几乎可以肯定的是，该基因产物将成为任何试图从宿主体液免疫系统引发中和抗体反应的疫苗的组成部分。我们在这里报告了几个HIV-1gp120变异体的测试，该变异体来自于一个初级分离株，该分离株似乎在诱导CD4+Help水平的免疫反应方面存在缺陷，从而在小动物中产生高亲和力的IgG抗体反应方面存在缺陷。限制有效免疫应答的因素包括(A)囊膜糖蛋白株的变异降低了功能性T细胞Help，(B)GP 120在不同细胞类型中的表达改变了糖基化模式，以及(C)GP 120本身的固有结构，这可能限制了在自然感染或佐剂肠外免疫期间有效T细胞Help的激发。在小动物和灵长类动物中设计和测试基于gpl20的免疫原时，应考虑这些限制因素和其他因素。
Efficient immune responses to HIV-1 gene products are essential elements to the development and design of an effective vaccine. Ideally, both humoral and cellular responses will be optimally elicited. It is therefore important to elucidate any factors that might limit the immumogenicity of HIV-1 proteins that are likely to be included in an effective vaccine. Since the HIV-1 exterior envelope glycoprotein gp 120 is a major target for neutralizing antibodies, it is a virtual certainty that this gene product will be a component of any vaccine that seeks to elicit neutralizing antibody responses from the host humoral immune system. We report here the testing of several HIV-1 gp 120 variants derived from a primary isolate that appears deficient in eliciting immune responses at both the level of CD4+ help and consequently in the generation of high-affinity IgG antibody responses in small animals. Factors limiting an effective immune response include (a) envelope glycoprotein strain variation decreasing functional T-cell help, (b) alteration of the glycosylation patterns of gp 120 by expression in different cell types, and (c) the native structure of gp 120 itself, which may limit the elicitation of effective T-cell help during natural infection or during parenteral immunization in adjuvant. Such limiting factors and others should be considered in the design and testing of gpl20-based immumogens in small animals and possibly in primates as well.