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Non-neurovirulent, genetically stable clone of poliovirus (Sabin type III vaccine strain)
T R Ubertini1, C Cioni, L Perini
1Sclavo Biopharmaceuticals, Siena, Italy.
Abstract:
A clone of poliovirus type III (TRU-3) was derived from the Sabin-3 vaccine strain by the cDNA:RNA hybrid molecular cloning method. The virus recovered was found to be considerably less neurovirulent for primates than its progenitor Sabin III vaccine strain. Upon serial passages in humans, TRU-3 did not increase its neurovirulence (unlike the Sabin strain) and maintained the base sequence of the attenuated strain in a critical part of the 5' region of the genome (unlike the Sabin strain). The substitution of TRU-3 clone for Sabin type III in oral polio vaccine could eliminate the vast majority of cases of vaccine-associated poliomyelitis.
Insights
A new poliovirus type III clone (TRU-3) shows reduced neurovirulence compared to the Sabin-3 vaccine. This attenuated strain could significantly decrease vaccine-associated poliomyelitis cases.
Area of Science:
- Virology
- Molecular Biology
- Vaccinology
Background:
- Poliovirus type III (Sabin-3) is used in oral polio vaccines.
- The Sabin-3 strain can cause vaccine-associated poliomyelitis.
- There is a need for safer polio vaccine strains.
Purpose of the Study:
- To develop a less neurovirulent poliovirus type III strain.
- To assess the neurovirulence and genetic stability of the TRU-3 clone.
Main Methods:
- Derivation of poliovirus type III clone TRU-3 from Sabin-3 using cDNA:RNA hybrid molecular cloning.
- Assessment of neurovirulence in primates.
- Serial passage in humans to evaluate neurovirulence changes.
- Analysis of the viral genome's 5' region sequence.
Main Results:
- The TRU-3 clone exhibited considerably lower neurovirulence in primates than the Sabin-3 strain.
- TRU-3 did not increase in neurovirulence after serial passages in humans.
- TRU-3 maintained the attenuated strain's base sequence in a critical 5' genomic region.
Conclusions:
- The TRU-3 clone represents a potentially safer alternative to the Sabin-3 vaccine strain.
- Substituting TRU-3 for Sabin type III in oral polio vaccines could largely eliminate vaccine-associated poliomyelitis.