Genetic Stability of Sabin 1 Strain of Poliovirus: Implications for Quality Control of Oral Poliovirus Vaccine

• Published in: Virology (New York, N.Y.) N.Y.), 1998-06, Vol.245 (2), p.183-187
• Main Authors: Rezapkin, Gennady V, Alexander, William, Dragunsky, Eugenia, Parker, Monica, Pomeroy, Kitty, Asher, David M, Chumakov, Konstantin M
• Format: Article
• Language: English
• Subjects: Animals; Genome, Viral; Haplorhini - virology; Poliovirus - genetics; Poliovirus Vaccine, Inactivated
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1998.9191

The Sabin vaccine strains of poliovirus, like all RNA viruses, exist as a quasispecies of genomic sequences whose composition can be altered during virus propagation. Since changes in vaccine virus during manufacture can enhance the neurovirulent potential of the vaccine, each monovalent lot of oral poliovirus vaccine (OPV) undergoes several tests to ensure consistency of manufacture, including the monkey neurovirulence test (MNVT). Recently, we proposed a new molecular approach for direct quantification of vaccine variants with neurovirulent potential as an alternative way to monitor consistency of OPV production. Analysis of the Sabin 1 genome allowed us to identify a limited number of specific loci that exhibit significant change during viral propagationin vitroandin vivo.Here we explore the possible roles of these changes and show that 7427-U→C and 7441-G→A alterations in the 3′-UTR of the Sabin 1 virus do not increase monkey neurovirulence. These, as well as our previous results, suggest that only mutations in the 5′-UTR play a significant role in the limited increase in Sabin 1 monkey neurovirulence observed after extended propagation of the virus beyond the passage level used in vaccine production. Our studies with high-passage batches of the Sabin 1 strain confirmed the stability of this strain, which retains acceptable levels of monkey neurovirulence even after serial passages at elevated temperature. Compared to the MNVT, molecular analysis of the genetic composition of Sabin 1 poliovirus provides a more sensitive analytical approach to monitor consistency of vaccine production.