Key result
The novel oral polio vaccine candidates nOPV1 and nOPV3 were significantly more attenuated than Sabin strains while maintaining comparable immunogenicity in mouse models.
Why the study?
Live attenuated oral polio vaccines evolve rapidly to reacquire virulence and form circulating vaccine-derived variants, risking polio re-emergence and creating a need for genetically stable vaccine candidates against types 1 and 3.
The novel nOPV1 and nOPV3 vaccine candidates are highly attenuated, genetically stable, and immunogenic in preclinical models, offering a potentially safer alternative to Sabin vaccines for poliovirus eradication.
OPV risks generating virulent variants in underimmunized populations; leaves open safer vaccine strategies for eradication.
Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence 1–3 resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.
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Yeh et al. (2023) studied Poliomyelitis. nOPV1 and nOPV3 vs. Sabin 1 and Sabin 3 was evaluated on Neurovirulence (PD50) and immunogenicity. The novel oral polio vaccine candidates nOPV1 and nOPV3 were significantly more attenuated than Sabin strains while maintaining comparable immunogenicity in mouse models.
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