Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160.
Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160.
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用来自接种牛痘 gp160 和重组 gp160 的捐赠者的外周血白细胞重建的 SCID 小鼠对人类免疫缺陷病毒 1 感染的抵抗力。
DOI：
10.1073/pnas.90.6.2443
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发表时间：
1993
影响因子：
11.1
通讯作者：
Greenberg,PD
中科院分区：
文献类型：
--
作者：
Mosier,DE;Gulizia,RJ;MacIsaac,PD;Corey,L;Greenberg,PD
用成人外周血白细胞重组的SCID小鼠(Hu-PBL-SCID小鼠)在二次免疫后产生抗原特异性的人类抗体反应，并可感染人类免疫缺陷病毒1(HIV-1)，这表明它们可能被证明是评估PBL供者接种后对HIV-1的保护性免疫的有用工具。HIV血清阴性志愿者用表达HIV-1LAV-1/Bru 160 kDa包膜糖蛋白的牛痘疫苗(痘苗gp160)免疫，然后加强注射重组gp160蛋白(Rgp160)。免疫后每隔4~72周用其PBL建立Hu-PBL-SCID小鼠，然后用10(2)-10(3)高同源HIV-1IIIB的最低动物感染量进行攻击。对照HU-PBL-SCID小鼠是由接种牛痘、明矾或乙肝疫苗的供体构建的。对病毒感染的保护被定义为通过培养没有HIV-1，并且在PCR扩增后没有检测到前病毒基因组。对照动物对艾滋病毒感染高度易感。相比之下，用痘苗gp160免疫并最近注射rgp160的四个供者中有三个的细胞重组的Hu-PBL-SCID小鼠，通过培养或聚合酶链式反应分析，没有显示出HIV-1感染的证据。随着rgp160注射时间的延长，疫苗衍生的Hu-PBL-SCID小鼠抵抗HIV-1感染的能力减弱。这些结果表明，这种HIV gp160免疫方案激发了潜在的保护性人体免疫反应，并表明了Hu-PBL-SCID模型在候选疫苗快速评估中的应用。
SCID mice reconstituted with adult human peripheral blood leukocytes (hu-PBL-SCID mice) make antigen-specific human antibody responses following secondary immunization and can be infected with human immunodeficiency virus 1 (HIV-1), suggesting that they might prove useful for evaluating protective immunity to HIV-1 following vaccination of PBL donors. HIV-seronegative volunteers were immunized with vaccinia expressing HIV-1LAV-1/Bru 160-kDa envelope glycoprotein (vaccinia gp160) and subsequently given booster injections of recombinant gp160 protein (rgp160). Their PBLs were used at intervals of 4-72 weeks after booster injections to construct hu-PBL-SCID mice, which were then challenged with 10(2)-10(3) minimal animal infectious doses of highly homologous HIV-1IIIB. Control hu-PBL-SCID mice were constructed from donors receiving vaccinia, alum, or hepatitis B vaccine. Protection against virus infection was defined as the absence of HIV-1 by culture and no detection of proviral genomes following PCR amplification. Control animals were highly susceptible to HIV infection. By contrast, hu-PBL-SCID mice reconstituted with cells from three of four donors immunized with vaccinia gp160 and recently injected with rgp160 showed no evidence of HIV-1 infection by culture or PCR assays. With increasing time after rgp160 injection, the ability of vaccine-derived hu-PBL-SCID mice to resist HIV-1 infection diminished. These results demonstrate that a potentially protective human immune response was stimulated by this HIV gp160 immunization protocol and show the utility of the hu-PBL-SCID model in the rapid evaluation of candidate vaccines.