Parren P W, Fisicaro P, Labrijn A F, Binley J M, Yang W P, Ditzel H J, Barbas C F, Burton D R
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Virol. 1996 Dec;70(12):9046-50. doi: 10.1128/JVI.70.12.9046-9050.1996.
Human antibody responses, or versions thereof, can be cloned as phage display libraries. In vaccine evaluation, the possibility therefore exists of challenging the human response in vitro, rather than in vivo, in order to assist in establishing the most promising vaccine leads. The characteristics of the antibodies retrieved directly indicate the strengths and weaknesses of the vaccine at the molecular level. We applied this approach to compare recombinant and native human immunodeficiency virus type 1 envelope preparations. We conclude that recombinant gp160, gp140, and, to a lesser extent, gp120 present epitopes around the CD4 binding site in a conformation different from that of the native multimer and contrary to expected vaccine requirements. Antibodies to the potently neutralizing b12 epitope were selected preferentially from an immune library by purified human immunodeficiency virus type 1 virions. This suggests that b12 is a major epitope on the virions, in contrast to recombinant envelope preparations, in which related, weakly neutralizing epitopes predominate. Although the majority of virions in the preparation used are expected to be noninfective, it appears that they predominantly express a native envelope configuration and would be able to elicit potent neutralizing antibodies.
人抗体应答或其变体可作为噬菌体展示文库进行克隆。因此，在疫苗评估中，存在在体外而非体内激发人应答的可能性，以协助确定最有前景的疫苗先导物。直接回收的抗体的特性在分子水平上直接表明了疫苗的优缺点。我们应用这种方法比较重组和天然1型人免疫缺陷病毒包膜制剂。我们得出结论，重组gp160、gp140以及程度稍轻的gp120在CD4结合位点周围呈现的表位，其构象不同于天然多聚体，且与预期的疫苗要求相反。通过纯化的1型人免疫缺陷病毒毒粒，从免疫文库中优先选择了对有效中和性b12表位的抗体。这表明，与重组包膜制剂不同，b12是毒粒上的主要表位，在重组包膜制剂中，相关的弱中和表位占主导。尽管所用制剂中的大多数毒粒预计无感染性，但它们似乎主要表达天然包膜构型，并且能够引发有效的中和抗体。
