Elicitation of immunity to HIV type 1 Gag is determined by Gag structure.
Elicitation of immunity to HIV type 1 Gag is determined by Gag structure.
复制标题
对 HIV 1 型 Gag 的免疫力的引发由 Gag 结构决定。
DOI：
10.1089/aid.2006.22.99
复制
发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Ross,TedM
中科院分区：
文献类型：
--
作者：
Young,KellyR;Ross,TedM
人类免疫缺陷病毒1型（HIV-1）的gaggene编码自组装成病毒颗粒的病毒蛋白。最初的Gag基因产物（衣壳、基质和核衣壳）在自然感染期间引发体液和细胞免疫反应，这些蛋白被包括在许多临床前和临床HIV/AIDS疫苗中。然而，这些蛋白质的结构（颗粒或可溶性）可能会影响疫苗接种期间引起的免疫力。在这项研究中，小鼠接种了四种不同的HIV-1 Gag疫苗，以比较相同的Gag免疫原以不同形式呈现给免疫系统所引发的免疫反应。将DNA质粒（pGag）在体内产生的颗粒与细胞内保留的相同蛋白质（pGagDMyr）所引起的免疫进行了比较。此外，比较了gagp55病毒样颗粒（VLPs）和可溶性非颗粒gagp55蛋白对抗Gag免疫的激发作用。细胞内保留的Gag蛋白增强了细胞反应，但几乎没有抗Gag抗体。相比之下，表达VLPs的DNA疫苗同时引发抗gag抗体和细胞反应。用纯化的Gagp55VLPs接种小鼠可引起强大的体液和细胞免疫应答，显著高于可溶性非颗粒性gagp55蛋白引起的免疫应答。总的来说，纯化的Gag颗粒有效地激发了最广泛和最高滴度的抗Gag免疫。Gag的结构形式影响引起的免疫反应，在设计艾滋病毒/艾滋病疫苗时应予以考虑。
Thegaggene of the human immunodeficiency virus type 1 (HIV-1) encodes for viral proteins that self-assemble into viral particles. The primary Gag gene products (capsid, matrix, and nucleocapsid) elicit humoral and cellular immune responses during natural infection, and these proteins are included in many preclinical and clinical HIV/AIDS vaccines. However, the structure (particulate or soluble) of these proteins may influence the immunity elicited during vaccination. In this study, mice were inoculated with four different HIV-1 Gag vaccines to compare the elicitation of immune responses by the same Gag immunogen presented to the immune system in different forms. The immunity elicited by particles producedin vivoby DNA plasmid (pGag) was compared to these same proteins retained intracellularly (pGagDMyr). In addition, the elicitation of anti- Gag immunity by Gagp55virus-like particles (VLPs) or soluble, nonparticulate Gagp55proteins was compared. Enhanced cellular responses, but almost no anti-Gag antibodies, were elicited with intracellularly retained Gag proteins. In contrast, DNA vaccines expressing VLPs elicited both anti-Gag antibodies and cellular responses. Mice vaccinated with purified Gagp55VLPs elicited robust humoral and cellular immune responses, which were significantly higher than the immunity elicited by soluble, nonparticulate Gagp55protein. Overall, purified particles of Gag effectively elicited the broadest and highest titers of anti-Gag immunity. The structural form of Gag influences the elicited immune responses and should be considered in the design of HIV/AIDS vaccines.