Shearer W T, Duliege A M, Kline M W, Hammill H, Minkoff H, Ammann A J, Chen S, Izu A, Mordenti J
Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Clin Diagn Lab Immunol. 1995 May;2(3):281-5. doi: 10.1128/cdli.2.3.281-285.1995.
Recombinant CD4-immunoglobulin G (rCD4-IgG) is a 98-kDa human immunoglobulin-like protein that is produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain. This hybrid molecule was given to human immunodeficiency virus (HIV)-infected pregnant women at the onset of labor by intravenous bolus at 1 mg/kg of body weight (group A; n = 3) and 1 week prior to and at the onset of labor by the same route and at the same dose (group B; n = 3). In addition to pharmacokinetic studies, safety in the mothers and infants was determined through routine chemistries, hematology, and urinalysis; immunologic and HIV infection statuses in the infants were assessed through lymphocyte cultures, p24 antigen level determination, culture of HIV from plasma, PCR, lymphocyte subset enumeration, quantitative immunoglobulin analysis, and lymphocyte proliferation. Thirty minutes after the rCD4-IgG injection, concentrations in maternal serum were 12 to 23 micrograms/ml. These concentrations declined slowly, with initial and terminal half-lives (mean +/- standard deviation) of 9.95 +/- 3.23 and 47.6 +/- 22.3 h, respectively. Infants were born 2.6 to 46.5 h after rCD4-IgG administration; concentrations of rCD4-IgG in cord blood ranged from 28 to 107 ng/ml. The half-life of rCD4-IgG in infants ranged from 5 to 29 h. These data demonstrate that the transfer of rCD4-IgG from the mother to the fetus is rapid and that newborns do not appear to have any difficulty eliminating rCD4-IgG. No safety concerns in mothers or infants were encountered. Although the study did not address the question of efficacy, none of the infants was HIV type 1 infected 36 months later. In summary, these findings document that bifunctional immune molecules can be transported across the placenta, and this general approach may be used in the future to block vertical transmission of HIV type 1.
重组CD4-免疫球蛋白G（rCD4-IgG）是一种98 kDa的人免疫球蛋白样蛋白，它通过将CD4的gp120结合结构域与人IgG1重链的Fc部分融合而产生。在分娩开始时，通过静脉推注以1 mg/kg体重的剂量将这种杂交分子给予感染人类免疫缺陷病毒（HIV）的孕妇（A组；n = 3），并在分娩前1周和分娩开始时通过相同途径给予相同剂量（B组；n = 3）。除了药代动力学研究外，还通过常规化学、血液学和尿液分析来确定母亲和婴儿的安全性；通过淋巴细胞培养、p24抗原水平测定、血浆HIV培养、聚合酶链反应（PCR）、淋巴细胞亚群计数、定量免疫球蛋白分析和淋巴细胞增殖来评估婴儿的免疫和HIV感染状况。rCD4-IgG注射30分钟后，母体血清中的浓度为12至23微克/毫升。这些浓度缓慢下降，初始半衰期和终末半衰期（平均值±标准差）分别为9.95±3.23小时和47.6±22.3小时。婴儿在给予rCD4-IgG后2.6至46.5小时出生；脐带血中rCD4-IgG的浓度范围为28至107纳克/毫升。rCD4-IgG在婴儿体内的半衰期为5至29小时。这些数据表明，rCD4-IgG从母亲向胎儿的转移很快，并且新生儿在清除rCD4-IgG方面似乎没有任何困难。未发现母亲或婴儿存在安全问题。尽管该研究未涉及疗效问题，但36个月后没有婴儿感染1型HIV。总之，这些发现证明双功能免疫分子可以穿过胎盘，并且这种通用方法未来可能用于阻断1型HIV的垂直传播。
