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

Cell Host Microbe. 2020 May 13;27(5):736-751.e8. doi: 10.1016/j.chom.2020.04.003. Epub 2020 Apr 23.


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.

Keywords: OPV2; Sabin 2p; live-attenuated vaccine; poliovirus; poliovirus eradication.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Chlorocebus aethiops
  • Disease Models, Animal
  • Female
  • Genetic Engineering / methods*
  • HeLa Cells
  • Humans
  • Immunogenicity, Vaccine
  • Male
  • Mice
  • Poliomyelitis / prevention & control
  • Poliovirus / genetics
  • Poliovirus Vaccine, Oral / administration & dosage
  • Poliovirus Vaccine, Oral / genetics*
  • Poliovirus Vaccine, Oral / immunology*
  • RNA, Viral / genetics
  • RNA-Dependent RNA Polymerase / genetics
  • Recombination, Genetic
  • Vaccination
  • Vaccines, Attenuated / genetics*
  • Vaccines, Attenuated / immunology*
  • Vero Cells
  • Virulence


  • Poliovirus Vaccine, Oral
  • RNA, Viral
  • Vaccines, Attenuated
  • polymerase 3Dpol, poliovirus
  • RNA-Dependent RNA Polymerase