Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160.

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. IMAGES:

经成人外周血白细胞（Peripheral Blood Leukocytes, PBL）重建的重症联合免疫缺陷（Severe Combined Immunodeficiency, SCID）小鼠（hu-PBL-SCID mice）在二次免疫后可产生抗原特异性人抗体应答，且可被人类免疫缺陷病毒1型（HIV-1）感染，这表明该模型可用于评估PBL供体接种疫苗后针对HIV-1的保护性免疫效果。研究人员对HIV血清阴性志愿者接种表达HIV-1LAV-1/Bru株160kDa包膜糖蛋白的痘苗病毒（vaccinia gp160），随后给予重组gp160蛋白（rgp160）加强免疫注射。在加强免疫后4~72周的不同时间点采集其PBL，用于构建hu-PBL-SCID小鼠，随后以10²~10³最小动物感染剂量的高同源性HIV-1IIIB毒株攻击这些小鼠。对照组hu-PBL-SCID小鼠的供体分别接种痘苗病毒、明矾佐剂或乙型肝炎疫苗。病毒感染防护的判定标准为：培养法未检测到HIV-1，且聚合酶链反应（Polymerase Chain Reaction, PCR）扩增未检出前病毒基因组。对照组动物对HIV感染高度易感。与之相比，4名接种vaccinia gp160并近期接受rgp160加强免疫的供体中，有3名的细胞重建的hu-PBL-SCID小鼠未通过培养法或PCR检测到HIV-1感染迹象。随着rgp160加强免疫后时间的推移，疫苗免疫供体来源的hu-PBL-SCID小鼠抵抗HIV-1感染的能力逐渐减弱。上述结果证明，该HIV gp160免疫方案可诱导具有潜在保护性的人免疫应答，同时证实了hu-PBL-SCID模型可用于候选疫苗的快速评估。IMAGES: