GENETIC STABILITY OF SABIN-1 STRAIN OF POLIOVIRUS - IMPLICATIONS FOR QUALITY-CONTROL OF ORAL POLIOVIRUS VACCINE

The Sabin Vaccine strains of poliovirus, like all RNA viruses, exist a s a quasispecies of genomic sequences whose composition can be altered during Virus propagation. Since changes in vaccine virus during manuf acture can enhance the neurovirulent potential of the vaccine, each mo novalent lot of oral poliovirus vaccine (OPV) undergoes several tests to ensure consistency of manufacture, including the monkey neurovirule nce test (MNVT). Recently, we proposed a new molecular approach for di rect quantification of vaccine Variants with neurovirulent potential a s an alternative way to monitor consistency of OPV production. Analysi s of the Sabin 1 genome allowed us to identify a limited number of spe cific loci that exhibit significant change during viral propagation in vitro and in vivo. Here we explore the possible roles of these change s and show that 7427-U-->C and 7441-G-->A alterations in the 3'-UTR or the Sabin 1 virus do not increase monkey neurovirulence. These, as we ll as our previous results, suggest that only mutations in the 5'-UTR play a significant role in the limited increase in Sabin 1 monkey neur ovirulence observed after extended propagation of the virus beyond the passage level used in vaccine production. Our studies with high-passa ge batches of the Sabin 1 strain confirmed the stability of this strai n, which retains acceptable levels of monkey neurovirulence even after serial passages at elevated temperature. Compared to the MNVT, molecu lar analysis of the genetic composition of Sabin 1 poliovirus provides a more sensitive analytical approach to monitor consistency of vaccin e production.