Andrus L, Prince A M, Bernal I, McCormack P, Lee D H, Gorny M K, Zolla-Pazner S
Lindsley F. Kimball Research Institute of the New York Blood Center, New York University Medical Center, New York 10021, USA.
J Infect Dis. 1998 Apr;177(4):889-97. doi: 10.1086/515251.
A monoclonal antibody (694/98-D) directed toward the V3 loop of human immunodeficiency virus type 1 (HIV-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-1LAI strain was obtained by preexposure administration of 1.32 mg/kg antibody. However, virus isolated from 1 mouse 3 weeks after passive immunization with 13.2 mg/kg antibody proved resistant to subsequent in vitro neutralization by 694/98-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 694/98-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.
一种针对人类免疫缺陷病毒1型（HIV-1）V3环的单克隆抗体（694/98-D），在用人外周血淋巴细胞重建的SCID小鼠（Hu-PBL-SCID）中进行了暴露前和暴露后预防评估。通过预先给予1.32mg/kg抗体，可获得对HIV-1LAI毒株50%的保护。然而，在用13.2mg/kg抗体进行被动免疫3周后，从1只小鼠分离出的病毒被证明对随后694/98-D的体外中和具有抗性。对克隆病毒的V3环序列分析显示，在694/98-D识别的线性核心表位内以及一个侧翼氨基酸处有氨基酸变化。在小鼠中对694/98-D进行暴露后预防的进一步评估显示，在病毒感染后15分钟给予694/98-D是有效的。然而，如果将治疗延迟到病毒接种后1小时，疗效会降至50%。这些研究指出了单克隆抗体被动免疫的一些潜在缺点。
