Developing genetically stable live-attenuated vaccine candidates against type 1 and 3 poliovirus

Abstract Vaccination with Sabin oral poliovirus vaccine (OPV) results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. However, as with any RNA virus, OPV can evolve rapidly . During replication, OPV strains can lose their attenuating mutations—polymorphisms in domain V of the 5′ untranslated region are critical to the reacquisition of virulence —and the reverted viruses can cause vaccine-associated paralytic polio in vaccine recipients or their immediate contacts. Also, circulation in under-immunized populations leads to further evolved viruses with higher transmission capacity, called circulating vaccine-derived polioviruses. These characteristics of OPV represent a significant risk of polio reemergence. A novel type 2 oral polio vaccine recently received authorization to respond to poliovirus outbreaks based on promising clinical data on genetic stability and immunogenicity. Here we report development of two additional vaccine candidates against types 1 and 3 poliovirus serotypes. The candidates were generated by replacing the capsid coding region of nOPV2 with those from Sabin 1 and Sabin 3. These chimeric viruses preserve all the nOPV2 documented characteristics concerning genetic stability. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and trivalent formulations and may contribute to the poliovirus eradication.