Yakovenko Maria L, Cherkasova Elena A, Rezapkin Gennady V, Ivanova Olga E, Ivanov Alexander P, Eremeeva Tatyana P, Baykova Olga Y, Chumakov Konstantin M, Agol Vadim I
A. N. Belozersky Institute of Physical-Chemical Biology, Moscow State University, Moscow 119899, Russia.
J Virol. 2006 Mar;80(6):2641-53. doi: 10.1128/JVI.80.6.2641-2653.2006.
The Sabin oral poliovirus vaccine (OPV) readily undergoes changes in antigenic sites upon replication in humans. Here, a set of antigenically altered descendants of the three OPV serotypes (76 isolates) was characterized to determine the driving forces behind these changes and their biological implications. The amino acid residues of OPV derivatives that lie within or close to the known antigenic sites exhibited a marked tendency to be replaced by residues characteristic of homotypic wild polioviruses, and these changes may occur very early in OPV evolution. The specific amino acid alterations nicely correlated with serotype-specific changes in the reactivity of certain individual antigenic sites, as revealed by the recently devised monoclonal antibody-based enzyme-linked immunosorbent assay. In comparison to the original vaccine, small changes, if any, in the neutralizing capacity of human or rabbit sera were observed in highly diverged vaccine polioviruses of three serotypes, in spite of strong alterations of certain epitopes. We propose that the common antigenic alterations in evolving OPV strains largely reflect attempts to eliminate fitness-decreasing mutations acquired either during the original selection of the vaccine or already present in the parental strains. Variability of individual epitopes does not appear to be primarily caused by, or lead to, a significant immune evasion, enhancing only slightly, if at all, the capacity of OPV derivatives to overcome immunity in human populations. This study reveals some important patterns of poliovirus evolution and has obvious implications for the rational design of live viral vaccines.
脊髓灰质炎减毒活疫苗（OPV）在人体复制过程中，其抗原位点很容易发生变化。在此，对三种OPV血清型的一组抗原性改变的子代病毒（76个分离株）进行了特征分析，以确定这些变化背后的驱动因素及其生物学意义。OPV衍生物中位于已知抗原位点内或附近的氨基酸残基，显示出被同型野生脊髓灰质炎病毒特征性残基取代的明显趋势，并且这些变化可能在OPV进化的早期就已发生。如最近设计的基于单克隆抗体的酶联免疫吸附测定所揭示的，特定的氨基酸改变与某些单个抗原位点反应性的血清型特异性变化密切相关。与原始疫苗相比，尽管某些表位发生了强烈改变，但在三种血清型高度分化的疫苗脊髓灰质炎病毒中，人或兔血清的中和能力仅有微小变化（如果有变化的话）。我们认为，进化中的OPV毒株常见的抗原性改变，很大程度上反映了消除在疫苗原始筛选过程中获得的或亲本毒株中已存在的适应性降低突变的尝试。单个表位的变异性似乎并非主要由显著的免疫逃逸引起，也不会导致显著的免疫逃逸，仅略微（如果有的话）增强了OPV衍生物克服人群免疫力的能力。这项研究揭示了脊髓灰质炎病毒进化的一些重要模式，对活病毒疫苗的合理设计具有明显的启示意义。
