Young Kelly R, Ross Ted M
Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.
AIDS Res Hum Retroviruses. 2006 Jan;22(1):99-108. doi: 10.1089/aid.2006.22.99.
The gag gene 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 produced in vivo by DNA plasmid (pGag) was compared to these same proteins retained intracellularly (pGag(DMyr)). In addition, the elicitation of anti- Gag immunity by Gag(p55) virus-like particles (VLPs) or soluble, nonparticulate Gag(p55) proteins 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 Gag(p55) VLPs elicited robust humoral and cellular immune responses, which were significantly higher than the immunity elicited by soluble, nonparticulate Gag(p55) protein. 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.
人类免疫缺陷病毒1型（HIV-1）的gag基因编码能自我组装成病毒颗粒的病毒蛋白。Gag基因的主要产物（衣壳、基质和核衣壳）在自然感染过程中引发体液免疫和细胞免疫反应，并且这些蛋白被纳入许多临床前和临床HIV/AIDS疫苗中。然而，这些蛋白的结构（颗粒状或可溶性）可能会影响疫苗接种过程中引发的免疫反应。在本研究中，给小鼠接种四种不同的HIV-1 Gag疫苗，以比较以不同形式呈递给免疫系统的相同Gag免疫原引发免疫反应的情况。将DNA质粒（pGag）在体内产生的颗粒引发的免疫反应与细胞内保留的相同蛋白（pGag(DMyr)）引发的免疫反应进行比较。此外，还比较了Gag(p55)病毒样颗粒（VLP）或可溶性、非颗粒状Gag(p55)蛋白引发抗Gag免疫反应的情况。细胞内保留的Gag蛋白引发了增强的细胞反应，但几乎没有抗Gag抗体。相比之下，表达VLP的DNA疫苗引发了抗Gag抗体和细胞反应。用纯化的Gag(p55) VLP接种的小鼠引发了强烈的体液免疫和细胞免疫反应，显著高于可溶性、非颗粒状Gag(p55)蛋白引发的免疫反应。总体而言，纯化的Gag颗粒有效地引发了最广泛和最高滴度的抗Gag免疫反应。Gag的结构形式会影响引发的免疫反应，在HIV/AIDS疫苗设计中应予以考虑。
