Lu Z, Asher D M, Levenbook I S, Chumakov K M
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20852, USA.
Virology. 1996 Jun 15;220(2):285-9. doi: 10.1006/viro.1996.0316.
Sabin strains of oral poliovirus vaccine (OPV) undergo limited genetic changes during replication in cell cultures, the gastrointestinal tract of vaccinees, and the central nervous system of monkeys. Some of these changes are associated with loss of attenuation markers. Here we report the dynamics of mutant accumulation in the Sabin strain of poliovirus type 3 inoculated intraspinally into monkeys. Thr --> lle reversion in amino acid 6 of VP1 (2493 C --> U) occurred within the first few days postinoculation (p.i.), but decreased on later days and completely disappeared by Day 17 p.i. 472 U --> C reversion in the 5'-untranslated region appeared to accumulate slower and by Day 17 completely substituted for the vaccine-type nucleotide at this site. These results indicate that experimental infection of the central nervous system of monkeys consists of early and late phases in which a different genetic constitution of the virus is favored. In several isolates one additional neurovirulent revertant was found: a Phe --> Ser at amino acid 91 of VP3 (2034 U --> C). Since this mutation was never detected in vaccine lots and is strongly selected against in cell cultures at temperatures below 38.5 degrees, it does not threaten the safety of OPV.
口服脊髓灰质炎病毒疫苗（OPV）的萨宾株在细胞培养物、疫苗接种者的胃肠道以及猴子的中枢神经系统中复制时会发生有限的基因变化。其中一些变化与减毒标记的丧失有关。在此，我们报告了经脊髓内接种到猴子体内的3型脊髓灰质炎病毒萨宾株中突变积累的动态情况。VP1第6位氨基酸（2493 C→U）的苏氨酸→异亮氨酸回复突变在接种后（p.i.）的头几天内出现，但在随后几天减少，并在接种后第17天完全消失。5'非翻译区的472 U→C回复突变似乎积累较慢，到第17天完全取代了该位点的疫苗型核苷酸。这些结果表明，猴子中枢神经系统的实验性感染包括早期和晚期阶段，在不同阶段病毒具有不同的遗传构成。在几个分离株中还发现了另一种神经毒力回复突变体：VP3第91位氨基酸（2034 U→C）的苯丙氨酸→丝氨酸。由于这种突变在疫苗批次中从未被检测到，并且在低于38.5摄氏度的细胞培养中受到强烈的选择抑制，因此它不会威胁OPV的安全性。
