A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection
A novel HIV-CCR5 receptor vaccine strategy in the control of mucosal SIV/HIV infection
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DOI：
10.1097/00002030-200401020-00003
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发表时间：
2004-01-02
期刊：
影响因子：
3.8
通讯作者：
Lehner, T
中科院分区：
文献类型：
--
作者：
Bogers, WMJM;Bergmeier, LA;Lehner, T
目的：开发一种新的SIV-CCR5受体疫苗策略，以保护SIV-CCR5受体疫苗通过阴道黏膜途径保护猕猴免受SIV感染。设计：该策略的基本原理是表达纯合子的Delta32 CCR5突变和相关的CC趋化因子上调、CCR5细胞表面表达下调和CCR5抗体对HIV感染具有保护作用。方法：由CCR5的3个胞外肽、转基因植物产生的HIV gp120 N端片段和重组SIV p27组成疫苗。这些基因与70000 M-r微生物热休克蛋白(HSP70)载体相关联。结果：免疫猕猴血清和阴道液抗体、IL-2和干扰素-γ产生细胞、巨噬细胞炎性蛋白(MIP)1β和MIP-1α(CCL4和CCL3)显著升高(P=0.01~0.05)。SHIV89.6P阴道攻击感染了所有猕猴，但24周的序贯分析显示，不同动物之间的病毒载量存在显著差异(P=0.05)。尽管SHIV89.6P在四只未免疫的猕猴中持续存在，但在八只免疫的猕猴中，有五只的病毒被清除或通过逆转录聚合酶链式反应检测不到病毒。免疫猕猴外周血中的CD_4细胞数显著高于未免疫猕猴(P
Objective: To develop a novel SIV-CCR5 receptor vaccine strategy that will protect macaques from SHIV infection by the vaginal mucosal route.Design: The rationale for this strategy is that humans who express the homozygous Delta32 CCR5 mutation and the associated upregulation of CC chemokines, the downmodulation of cell-surface expression of CCR5 and antibodies to CCR5 are protected against HIV infection.Methods: A vaccine was prepared consisting of three extracellular peptides of CCR5, an N-terminal HIV gp120 fragment generated in transgenic plants and recombinant SIV p27. These were linked to the 70 000 M-r microbial heat shock protein (HSP70) carrier. The vaccine was administered (X3) either by the vaginal mucosal route or by targeting the proximity of the draining iliac lymph nodes.Results: Serum and vaginal fluid IgG and IgA antibodies, IL-2 and IFN-gamma-producing cells, and macrophage-inflammatory protein (MIP) 1beta and MIP-1alpha (CCL4 and CCL3) were significantly raised in immunized macaques (P=0.01-0.05). Vaginal challenge with SHIV89.6P infected all macaques, but sequential analysis over 24 weeks showed a significant variation in viral loads between the animals (P=0.05). Whereas SHIV89.6P persisted in the four unimmunized macaques, in five of the eight immunized macaques the virus was cleared or became undetectable by reverse transcriptase-polymerase chain reaction. The CD4 cell counts in the immunized macaques were significantly higher than those in unimmunized animals (P