Assessing the stability of polio eradication after the withdrawal of oral polio vaccine

Abstract

The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population immunity will be required to ensure the stability of polio eradication.

The Early Evolution of Oral Poliovirus Vaccine Is Shaped by Strong Positive Selection and Tight Transmission Bottlenecks

“…We identified 111 samples with > 200× coverage ( Figure 1 C, red points), 81 samples with > 500× coverage, and 48 samples with > 1000× coverage across the genome, based on averages across a 50-bp sliding window. The majority of samples that yielded at least partial OPV2 genome coverage were collected in the first 2 months following vaccination ( Figure 1 C), which is consistent with the known shedding duration of Sabin type 2 ( Famulare et al., 2018 ). Most individuals were represented by only one sample, although a subset of individuals had multiple longitudinal samples with at least partial genome data ( Figure S1 ).…”

“…Rather than antigenic escape, we suggest that these mutations lead to improved within-host replication and, therefore, greater shedding and transmission. Epidemiologic data suggest that at some unknown point in cVDPV evolution, OPV achieves a level of transmissibility that is similar to that of wild polioviruses ( Famulare et al., 2018 ; Jenkins et al., 2010 ; Duintjer Tebbens et al., 2013 ). Selection for phenotypes related to this increase in transmissibility, like enteric replication and shedding, are likely the earliest pressures the virus faces ( Bull et al., 2018 ).…”

“…Transmission, both later on in infections when viral load is low and to more distant community contacts, was uncommon in this highly immune population ( Taniuchi et al., 2017 ). Furthermore, bottlenecks may be larger in populations with lower background immunity and higher fecal-oral exposure where naturally acquired doses are likely higher ( Famulare et al., 2018 ), which would allow positive selection among minor variants to act.…”

Assessing the Risk of Vaccine-derived Outbreaks After Reintroduction of Oral Poliovirus Vaccine in Postcessation Settings

“…Given these limitations in data, we made a number of simplifying assumptions about poliovirus natural history and transmission, consistent with previously published models [ 10 , 13 , 22 ], to create a relatively parsimonious model that would improve parameter identifiability and avoid overfitting [ 23 ]. We modeled only 2 age groups (<5 and >5 years), did not model assortative mixing behaviors outside the household, and assumed that intestinal immunity generated during the study period prevented reinfection during the simulation period.…”

Identification of genes and pathways in human antigen‐presenting cell subsets in response to polio vaccine by bioinformatical analysis

“…The oral poliovirus vaccine (OPV) contains the live-attenuated poliovirus that induces immunity but can paralyze vaccinated recipients and generate an outbreak of vaccine-derived poliovirus. 2 The OPV replicates and activates the adaptive immune system by antigen-presenting cells (APCs), which migrate to lymphoid organs to present the antigen to T and B cells. [3][4][5] The IPV does not replicate and is safer than the OPV; however, the IPV activates innate responses only at their site of injection.…”