Codon Deoptimized (CD) Poliovirus Seed Strains for Use in an Inactivated Poliovirus Vaccine

Polio is a disabling and potentially fatal infectious disease. Sabin Oral Poliovirus Vaccine (OPV) and Salk Inactivated Poliovirus Vaccine (IPV) have been crucial in the global poliovirus eradication efforts and substantial decrease in disease incidence rates. However, recent findings showed that Sabin OPV strains, due to their genetic instability, may revert to virulence and spread among communities, resulting in circulating vaccine-derived poliovirus (cVDPV). Salk IPV, which is made by inactivating live poliovirus, poses a potential threat of viral containment breach (spill/exposure) during the manufacturing process. Salk IPV is also limited by its inability to confer intestinal immunity, a factor that is crucial to stop fecal-oral viral transmission, especially in developing countries with poor sanitation and limited clean drinking water. A safer, genetically stable vaccine candidate is highly essential for the containment of poliovirus breach, whether it would occur during the manufacturing process or due to cVDPV spread, and in achieving complete eradication of the disease.

CDC inventors discovered that replacing one or more natural (or native) codons in a pathogen with synonymous un-preferred codons can decrease replicative fitness of the pathogen, thereby attenuating (decreasing the virulence of) the pathogen. Building on this, CDC researchers applied the previously patented codon deoptimization (CD) technology to the Sabin oral poliovirus vaccine (OPV) strains to develop attenuated poliovirus strains with enhanced genetic stability. These attenuated strains were then used as seed strains for a new Sabin inactivated poliovirus vaccine (sIPV) that is more stable and has less likelihood of reverting back to virulence. These modified sIPV candidates, while antigenically equivalent to the currently used Sabin OPV, offer safer methods for vaccine manufacture and viral breach containment. Researchers produced CD seed strains of all three poliovirus serotypes for Sabin OPV. As polio eradication progresses, more poliovirus containment requirements may be enacted.