Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence

TLDR

The live‑attenuated oral poliovirus vaccine (OPV) induces mucosal and systemic immunity, protects against disease, and is the main tool for ending poliovirus circulation, but its capacity to revert to virulence poses a re‑emergence risk if immunization stops. The study reports the development of a genetically more stable poliovirus type 2 vaccine strain (nOPV2) that is less likely to regain virulence than the original Sabin 2 strain. The authors engineered nOPV2 by introducing stabilizing mutations in the 5′ untranslated region, 2C coding region to block recombination, and 3D polymerase to restrict viral adaptability. Preclinical and clinical studies show that nOPV2 is immunogenic, supporting its potential to enable complete poliovirus eradication.

Abstract

The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from disease and limits poliovirus spread. Accordingly, vaccination with OPV is the primary strategy used to end the circulation of all polioviruses. However, the ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. Here, we report the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. We introduced modifications within at the 5' untranslated region of the Sabin2 genome to stabilize attenuation determinants, 2C coding region to prevent recombination, and 3D polymerase to limit viral adaptability. Prior work established that nOPV2 is immunogenic in preclinical and clinical studies, and thus may enable complete poliovirus eradication.