Derby Nina R, Gray Sean, Wayner Elizabeth, Campogan Dwayne, Vlahogiannis Giorgos, Kraft Zane, Barnett Susan W, Srivastava Indresh K, Stamatatos Leonidas
Seattle Biomedical Research Institute, Seattle, WA 98109, USA; Department of Pathobiology, University of Washington, Seattle, WA 98109, USA.
Virology. 2007 Sep 30;366(2):433-45. doi: 10.1016/j.virol.2007.05.020. Epub 2007 Jun 8.
Eleven anti-HIV Env monoclonal antibodies (MAbs) were isolated from mice immunized with soluble Env proteins derived from the clade B Env, SF162, or DeltaV2 (a derivative of SF162 lacking the V2 loop). All six anti-gp120 MAbs studied, neutralized SF162 and their activities were dependent by the glycosylation patterns of the V1, V2 or V3 loops. Only one anti-gp120 MAb (an anti-V3 MAb) displayed cross-neutralizing activity, which was influenced by the type of V1 loop present on the target heterologous viruses. None of the five anti-gp41 MAbs studied displayed anti-SF162 neutralizing activity. Our studies indicate that the current limitation of soluble HIV Env gp140 immunogens to elicit robust cross-reactive neutralizing antibody responses is not only due to the elicitation of high titers of homologous antibodies but also due to the elicitation of antibodies whose epitopes are naturally occluded, or not present, on the virion-associated Env.
从用源自B亚型Env、SF162或DeltaV2（SF162缺失V2环的衍生物）的可溶性Env蛋白免疫的小鼠中分离出11种抗HIV Env单克隆抗体（MAb）。所研究的所有六种抗gp120 MAb均能中和SF162，其活性取决于V1、V2或V3环的糖基化模式。只有一种抗gp120 MAb（一种抗V3 MAb）表现出交叉中和活性，这受到靶异源病毒上存在的V1环类型的影响。所研究的五种抗gp41 MAb均未表现出抗SF162中和活性。我们的研究表明，目前可溶性HIV Env gp140免疫原引发强大的交叉反应性中和抗体反应的局限性不仅是由于引发了高滴度的同源抗体，还由于引发了其表位在病毒体相关Env上自然被封闭或不存在的抗体。
