Sakurai H, Williamson R A, Crowe J E, Beeler J A, Poignard P, Bastidas R B, Chanock R M, Burton D R
Departments of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Virol. 1999 Apr;73(4):2956-62. doi: 10.1128/JVI.73.4.2956-2962.1999.
A number of antibodies generated during human respiratory syncytial virus (RSV) infection have been cloned by the phage library approach. Antibodies reactive with an immunodominant epitope on the F glycoprotein of this virus have a high affinity for affinity-purified F antigen. These antibodies, however, have a much lower affinity for mature F glycoprotein on the surface of infected cells and are nonneutralizing. In contrast, a potent neutralizing antibody has a high affinity for mature F protein but a much lower affinity for purified F protein or F protein in viral lysates. The data indicate that at least two F protein immunogens are produced during natural RSV infection: immature F, found in viral lysates, and mature F, found on infected cells or virions. Binding studies with polyclonal human immunoglobulin G suggest that the antibody responses to the two immunogens are of similar magnitudes. Competitive binding studies suggest that overlap between the responses is relatively limited. A mature envelope with an antigenic configuration different from that of the immature envelope has an evolutionary advantage in that the infecting virus is less subject to neutralization by the humoral response to the immature envelope that inevitably arises following lysis of infected cells. Subunit vaccines may be at a disadvantage because they most often resemble immature envelope molecules and ignore this aspect of viral evasion.
通过噬菌体文库方法已克隆出人类呼吸道合胞病毒（RSV）感染期间产生的多种抗体。与该病毒F糖蛋白上的免疫显性表位发生反应的抗体对亲和纯化的F抗原有高亲和力。然而，这些抗体对感染细胞表面的成熟F糖蛋白的亲和力要低得多，且无中和作用。相比之下，一种有效的中和抗体对成熟F蛋白有高亲和力，但对纯化的F蛋白或病毒裂解物中的F蛋白亲和力要低得多。数据表明，在自然RSV感染期间产生至少两种F蛋白免疫原：病毒裂解物中发现的未成熟F和感染细胞或病毒粒子上发现的成熟F。用多克隆人免疫球蛋白G进行的结合研究表明，对这两种免疫原的抗体反应强度相似。竞争性结合研究表明，反应之间的重叠相对有限。具有与未成熟包膜不同抗原构型的成熟包膜具有进化优势，即感染病毒较少受到对未成熟包膜的体液反应的中和作用，这种反应在感染细胞裂解后不可避免地会出现。亚单位疫苗可能处于劣势，因为它们最常类似于未成熟包膜分子，而忽略了病毒逃避的这一方面。
