Passive immunization with a human immunodeficiency virus type 1-neutralizing monoclonal antibody in Hu-PBL-SCID mice: Isolation of a neutralization escape variant
Passive immunization with a human immunodeficiency virus type 1-neutralizing monoclonal antibody in Hu-PBL-SCID mice: Isolation of a neutralization escape variant
复制标题
DOI：
10.1086/515251
复制
发表时间：
1998-04-01
影响因子：
6.4
通讯作者：
Zolla-Pazner, S
中科院分区：
文献类型：
--
作者：
Andrus, L;Prince, AM;Zolla-Pazner, S
在用人外周血淋巴细胞（Hu-PBL-SCID）重建的SCID小鼠中，评估了针对人类免疫缺陷病毒1型（HTV-1）V3环的单克隆抗体（694/98-D）在暴露前和暴露后的预防作用。用13.2mg/kg抗体被动免疫1只小鼠3周后，分离到的病毒对693/98-D的体外中和有抵抗力。克隆病毒的V3环序列分析揭示了由694/98-D识别的线性核心表位内和一个侧翼氨基酸中的氨基酸变化。进一步评价693/98-D在小鼠中的暴露后预防作用显示，在病毒感染后15分钟给予694/98-D是有效的。然而，如果治疗延迟至病毒接种后1小时，疗效下降至50%。这些研究指出了单克隆抗体被动免疫的一些潜在缺点。
A monoclonal antibody (694/98-D) directed toward the V3 loop of human immunodeficiency virus type 1 (HTV-1) was evaluated for pre-and postexposure prophylaxis in SCID mice reconstituted with human peripheral blood lymphocytes (Hu-PBL-SCID). Fifty percent protection against the HIV-1(LAI) strain was obtained by preexposure administration of 1.32 mg/kg antibody, However, virus isolated from I mouse 3 weeks after passive immunization with 13.2 mg/kg antibody proved resistant to subsequent in vitro neutralization by 693/98-D. V3 loop sequence analysis of cloned virus revealed amino acid changes within the linear core epitope recognized by 694/98-D and in one flanking amino acid. Further evaluation of 693/98-D for postexposure prophylaxis in mice revealed that 694/98-D was effective when given 15 min after virus. However, efficacy declined to 50% if treatment was delayed to 1 h after virus inoculation. These studies point out some potential drawbacks of passive immunization with monoclonal antibodies.