Abstract

The search for a human immunodeficiency virus (HIV) vaccine has spanned nearly four decades without much success. A much needed paradigm shift can be found in the abnormally high levels of intrinsic disorder in the outer shells of HIVs, the hepatitis C virus (HCV), and herpes simplex viruses (HSVs), for which successful vaccines have not been established. On the other hand, this feature (high levels of intrinsic disorder in the outer shells) is completely absent in classic viruses for which effective vaccines are found, such as the rabies virus. The motions arising from the disordered outer shell result in the inability of antibodies to bind tightly to the polysaccharides on the viral surface proteins, and, therefore, induce inadequate immune response. Experiments conducted by the legendary Avery Oswald in the 1920s form the theoretical underpinning of this new model. Failures of the vaccines based on the HIV glycoprotein Gp120 and other vaccines can be traced back to the lack of understanding of the important roles of shell disorder in a “Trojan-horse” immune evasion mechanism utilized by the virus.

Communicated by Ramaswamy H. Sarma

摘要

寻找人类免疫缺陷病毒（HIV）疫苗的过程已经跨越了近四十年，但没有取得太大的成功。在尚未建立成功疫苗的HIV，丙型肝炎病毒（HCV）和单纯疱疹病毒（HSV）外壳中异常高水平的内在疾病中，可以找到急需的范例转变。另一方面，在发现有效疫苗的经典病毒（如狂犬病病毒）中，完全没有这种功能（外壳中高水平的内在失调）。由无序外壳引起的运动导致抗体无法与病毒表面蛋白上的多糖紧密结合，因此导致免疫应答不足。传奇的艾利·奥斯瓦尔德（Avery Oswald）在1920年代进行的实验构成了这种新模型的理论基础。基于HIV糖蛋白Gp120的疫苗和其他疫苗的失败可归因于对壳病在病毒利用的“特洛伊木马”免疫逃逸机制中的重要作用缺乏了解。

由Ramaswamy H.Sarma沟通