Effect of different promoters on immune response elicited by HIV-1 gag/nev multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina
Effect of different promoters on immune response elicited by HIV-1 gag/nev multigenic DNA vaccine in Macaca mulatta and Macaca nemestrina
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DOI：
10.1016/s0264-410x(99)00569-1
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发表时间：
2000-05-22
期刊：
影响因子：
5.5
通讯作者：
Khan, AS
中科院分区：
文献类型：
--
作者：
Galvin, TA;Muller, J;Khan, AS
pCMV-NLDelta pol 和 pAKV-NLDelta pol 分别在人巨细胞病毒 (CMV) 立即早期 (IE) 启动子：增强子和内源 AKV 鼠白血病病毒长末端重复 (LTR) 的调节下表达人类免疫缺陷病毒 1 型 (HIV-1) gag 和 env。对猕猴中直接 DNA 注射 pCMV-NLDelta pol 和 pAKV-NLDelta pol 引起的免疫反应的分析表明，体液和 T 细胞增殖反应的产生与疫苗 DNA 的启动子强度直接相关。在 Mucaca mulatta 中，pCMV-NLDelta pol 比 pAKV-NLDelta pol 使用更少的 DNA 和更少的注射次数，产生了更强的体液反应和对 Gag 和 Env 的 T 细胞增殖反应。类似地，在猕猴中，pCMV-NLDelta pol 引发了高体液反应，这种反应长期持续且可增强。一般来说，注射大量的pAKV-NLDelta pol不能产生与pCMV-NLDelta pol相当的抗体水平。然而。向对照动物注射大量载体 DNA，产生了针对 HIV-1 的通用酶联免疫吸附测定 (ELISA) 反应性。结果表明，通过增加疫苗 DNA 剂量无法产生针对 HIV-1 的高免疫反应，可能需要通过包含强启动子或使用其他增强剂来实现 DNA 的高蛋白表达。此外，随着 DNA 剂量的增加，可能会出现安全问题，这可能需要进一步的研究。由爱思唯尔科学有限公司出版
pCMV-NLDelta pol and pAKV-NLDelta pol expressed human immunodeficiency virus type 1 (HIV-1) gag and env under the regulation of the human cytomegalovirus (CMV) immediate-early (IE) promoter:enhancer and the endogenous AKV murine leukemia viral long terminal repeat (LTR), respectively. Analysis of the immune responses elicited by direct DNA injection of pCMV- NLDelta pol and pAKV-NLDelta pol in macaques indicated that generation of the humoral and T-cell proliferative responses correlated directly with the promoter strength of the vaccine DNAs. In Mucaca mulatta, pCMV-NLDelta pol generated stronger humoral responses and T-cell proliferative responses to Gag and Env using less DNA and fewer number of injections than pAKV-NLDelta pol Similarly, in Macaca nemestrina pCMV-NLDelta pol elicited high humoral responses, which persisted long-term and were boostable. Injection of large amounts of pAKV-NLDelta pol, in general, failed to produce antibody levels comparable to pCMV-NLDelta pol. However. injection of a control animal with large amounts of vector DNA produced a generalized enzyme-linked immunosorbent assay (ELISA) reactivity to HIV-1. The results indicated that generation of high immune responses to HIV-1 cannot be achieved by increasing the vaccine DNA dose and may require high protein expression from the DNA by including a strong promoter or by the use of other boosting agents. Furthermore, safety concerns may arise with increasing the DNA dose that could need additional investigation. Published by Elsevier Science Ltd.