Vincent Nadine, Tardy Jean-Claude, Livrozet Jean-Michel, Lucht Frédéric, Frésard Anne, Genin Christian, Malvoisin Etienne
Groupe Immunité des Muqueuses et Agents Pathogènes, Faculty of Medicine of Saint-Etienne, France.
J Acquir Immune Defic Syndr. 2005 Mar 1;38(3):254-62.
The anti-HIV drug T20 is a synthetic peptide derived from the HR2 region of HIV-1 gp41. T20 contains the sequence ELDKWA, which binds the broadly neutralizing antibody 2F5. Using plates coated with T20 or with synthetic peptides and recombinant proteins representing gp120 or gp41 domains, this study investigated by enzyme-linked immunosorbent assay the levels of antibodies directed to the gp160 molecule in patients treated with T20. Analysis of sera obtained before and after administration of T20 indicated that the levels of antibodies directed to T20, to MBP44, a maltose binding protein representing the HR2 region, and to 4765, a synthetic peptide containing the sequence ELDKWA, fell following administration of T20, while the levels of antibodies directed to other regions of gp41 ectodomain and to gp120 remained stable. The decline observed was independent of the viral load and of the total IgG concentration. Follow-up studies with sera obtained from HIV-1-seropositive patients naive to T20 indicated no decline in the level of antibodies directed to HR2 and other regions of gp160. Analysis of sera obtained from a patient after 2 months of T20 treatment interruption showed a level of antibodies to the HR2 region similar to that measured before administration of T20. The addition of increasing amounts of T20 to sera from T20-naive patients decreased the level of serum antibodies against peptide 4765, T20, and MBP44. The observation of antibody depletion by T20 suggests that anti-gp41 antibodies may interfere with T20 treatment by forming T20-antibody complexes.
抗艾滋病病毒药物T20是一种源自HIV-1 gp41 HR2区域的合成肽。T20含有ELDKWA序列，该序列可结合广泛中和抗体2F5。本研究使用包被有T20或代表gp120或gp41结构域的合成肽及重组蛋白的平板，通过酶联免疫吸附测定法研究了接受T20治疗的患者中针对gp160分子的抗体水平。对T20给药前后获得的血清分析表明，给药后，针对T20、针对代表HR2区域的麦芽糖结合蛋白MBP44以及针对含有ELDKWA序列的合成肽4765的抗体水平下降，而针对gp41胞外结构域其他区域及gp120的抗体水平保持稳定。观察到的下降与病毒载量和总IgG浓度无关。对未接受过T20治疗的HIV-1血清阳性患者的血清进行随访研究表明，针对gp160的HR2及其他区域的抗体水平没有下降。对一名患者在中断T20治疗2个月后获得的血清分析显示，针对HR2区域的抗体水平与给药前测得的水平相似。向未接受过T20治疗的患者的血清中添加越来越多的T20会降低血清中针对肽4765、T20和MBP44的抗体水平。T20导致抗体耗竭的观察结果表明，抗gp41抗体可能通过形成T20 - 抗体复合物干扰T20治疗。
