Updated Characterization of Outbreak Response Strategies for 2019-2029: Impacts of Using a Novel Type 2 Oral Poliovirus Vaccine Strain

Abstract

Delays in achieving the global eradication of wild poliovirus transmission continue to postpone subsequent cessation of all oral poliovirus vaccine (OPV) use. Countries must stop OPV use to end all cases of poliomyelitis, including vaccine-associated paralytic polio (VAPP) and cases caused by vaccine-derived polioviruses (VDPVs). The Global Polio Eradication Initiative (GPEI) coordinated global cessation of all type 2 OPV (OPV2) use in routine immunization in 2016 but did not successfully end the transmission of type 2 VDPVs (VDPV2s), and consequently continues to use type 2 OPV (OPV2) for outbreak response activities. Using an updated global poliovirus transmission and OPV evolution model, we characterize outbreak response options for 2019-2029 related to responding to VDPV2 outbreaks with a genetically stabilized novel OPV (nOPV2) strain or with the currently licensed monovalent OPV2 (mOPV2). Given uncertainties about the properties of nOPV2, we model different assumptions that appear consistent with the evidence on nOPV2 to date. Using nOPV2 to respond to detected cases may reduce the expected VDPV and VAPP cases and the risk of needing to restart OPV2 use in routine immunization compared to mOPV2 use for outbreak response. The actual properties, availability, and use of nOPV2 will determine its effects on type 2 poliovirus transmission in populations. Even with optimal nOPV2 performance, countries and the GPEI would still likely need to restart OPV2 use in routine immunization in OPV-using countries if operational improvements in outbreak response to stop the transmission of cVDPV2s are not implemented effectively.

Keywords: Dynamic modeling; outbreak response; polio.

Fig. 1.

Poliovirus genome: (a) Genomic organization and primary translational open reading frame and processed proteins for polioviruses and (b) Key attenuating mutations for each OPV type (nucleotide changes shown below the line and amino acid changes shown above the line).

Fig. 2:

Assumed effect of reversion of OPV-related viruses by stage for the (a) relative basic reproductive number (R₀) and (b) paralysis-to-infection ratio (PIR)

Fig. 3.

Schematic representation of the genetic changes introduced into different nOPV2 candidate strains (based on (Konopka-Anstadt et al., 2020) (Yeh et al., 2020)). All genomic changes that characterize the Candidate strain are highlighted in red color and/or font.

Fig. 4.

Theoretical pathway for loss of engineered changes and reversion of attenuation for nOPV2 candidate 1 by serial recombination events during replication and transmission. The resulting species (Progeny 2) is a strain that has lost all attenuating mutations compared with nOPV2.

Fig. 5.

Characterization of model inputs assumed for nOPV2 candidate 1 compared to mOPV2 for the (a) relative basic reproductive number (R₀) and (b) paralysis-to-infection ratio (PIR)

Fig. 6.

Expected value of annual serotype 2 paralytic cases for 2019–2029 based on 100 iterations for modeled scenarios that use different vaccine options to respond to outbreaks: mOPV2 through 2024 then IPV (RC2), mOPV2 for outbreak response for the full time horizon (RC3), or using nOPV2 starting in 2021 with different characteristics: (a) Incidence of cVDPV2s (“No reversion, no VAPP” and “No Reversion, same VAPP” lines overlap) (b) Incidence of type 2 VAPP (“No reversion,no VAPP” and “Some reversion, lower VAPP” lines overlap)