Abstract
The life-attenuated Sabin oral poliovirus vaccine (OPV), created over 60 years ago, replicate efficiently in the vaccinee’s gut and, therefore, elicits robust mucosal and systemic immunity, which limits poliovirus spread. Accordingly, OPV has been used in the context of the Global Polio Eradication Initiative, which aims to end the circulation of all polioviruses. However, the program has met a significant hurdle imposed by the ability of OPV to evolve to regain transmissibility and virulence. This represents a risk of widespread polio re-emergence should immunization cease. We exploited molecular features of poliovirus replication to develop a safer, genetically stable, strain by limiting its ability to increase fitness and regain neurovirulence. This novel attenuated poliovirus strain is immunogenic in preclinical and clinical tests and may enable completion of poliovirus eradication as well as pave the way for the rational design of effective and safe vaccines for polio-related pathogens.
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