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[来自重组卡介苗载体候选疫苗的嵌合可溶性蛋白对HIV-1的保护性免疫反应诱导]

[Induction of protective immune responses by a chimeric soluble protein from a recombinant BCG vector candidate vaccine to HIV-1].

作者信息

Honda M, Kitamura K, Okamoto Y, Watanabe K, Yoshizaki H, Fukushima Y, Naganawa S, Miyamoto G, Someya K, Yamada K

机构信息

National Institute of Health, Tokyo.

出版信息

Rinsho Ketsueki. 1995 May;36(5):435-41.

PMID:7783347
Abstract

We have been isolated HIV strains from blood specimens of HIV infected individuals in Japan for these 6 years. The number of specimens tested reached approximately 1,700 that ninety percent of them were from hemophiliacs repeatedly injected blood products from the United States. More than 300 of field HIV were successfully isolated from the samples. The isolation rates has decreased to 30 percent in 1993 from 40 percent in 1992, suggesting that treatment with anti-HIV drugs such as AZT and/or ddI may be effective to HIV-infected individuals. Further, both of the viral and genomic sequences of HIV were classified to be clade B virus. The clinical isolates that expressed IHIGPGRAFY sequence at the center of the HIV-V3 domain were found to be neutralized by an anti-clade B-V3 monoclonal antibody, mu 5.5. By individual levels, when asymptomatic seropositives have progressed to disease-states, neutralization core motif of GPGR in approximately 6% of the viruses has changed to GPGG and hydrophilic amino acid changed to hydrophobic amino acid, correlating the loss of binding activity to PND-peptide of Japanese Consensus virus. Further, rapid progressors to HIV-induced diseases showed decreased activity of the binding antibody. By using the Japanese consensus sequence of HIV-1, we successfully constructed chimeric protein secretion vectors by selecting an appropriate insertion site of a carrier protein, and established the PND-peptide secretion system in BCG. The recombinant BCG inoculated guinea pigs were initially screened by delayed-type hypersensitivity (DTH) skin reactions to the PND peptide followed by passive transfer of the DTH by the systemic route.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

在过去6年里,我们从日本HIV感染者的血液样本中分离出了HIV毒株。检测的样本数量约为1700份,其中90%来自反复注射美国血液制品的血友病患者。从这些样本中成功分离出了300多株HIV毒株。分离率从1992年的40%降至1993年的30%,这表明使用齐多夫定(AZT)和/或双脱氧肌苷(ddI)等抗HIV药物治疗可能对HIV感染者有效。此外,HIV的病毒和基因组序列均被归类为B亚型病毒。发现在HIV-V3结构域中心表达IHIGPGRAFY序列的临床分离株可被抗B亚型-V3单克隆抗体mu 5.5中和。在个体水平上,当无症状血清阳性者进展到疾病状态时,约6%的病毒中GPGR的中和核心基序已变为GPGG,亲水性氨基酸变为疏水性氨基酸,这与对日本共识病毒PND肽的结合活性丧失相关。此外,HIV诱导疾病的快速进展者显示结合抗体的活性降低。通过使用HIV-1的日本共识序列,我们通过选择载体蛋白的合适插入位点成功构建了嵌合蛋白分泌载体,并在卡介苗中建立了PND肽分泌系统。对接种重组卡介苗的豚鼠首先通过对PND肽的迟发型超敏反应(DTH)皮肤反应进行筛选,然后通过全身途径进行DTH的被动转移。(摘要截断于250字)

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