Inactivated Poliovirus Vaccine: Recent Developments and the Tortuous Path to Global Acceptance.

Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities.

Modelling the spread of serotype-2 vaccine derived-poliovirus outbreak in Pakistan and Afghanistan to inform outbreak control strategies in the context of the COVID-19 pandemic.

BACKGROUND: Since July 2019, Pakistan and Afghanistan have been facing an outbreak of serotype-2 circulating vaccine derived poliovirus (cVDPV2) in addition to continued transmission of serotype-1 wild poliovirus (WPV1) and SARS-CoV-2 in 2020. Understanding the risks of cVDPV2 transmission due to pause of global vaccination efforts and the impact of potential vaccination response strategies in the current context of COVID-19 mitigation measures is critical. METHODS: We developed a stochastic, geographically structured mathematical model of cVDPV2 transmission which captures both mucosal and humoral immunity separately and allows for reversion of serotype-2 oral polio vaccine (OPV2) virus to cVDPV2 following vaccine administration. The model includes geographic heterogeneities in vaccination coverage, population immunity and population movement. The model was fitted to historic cVDPV2 cases in Pakistan and Afghanistan between January 2010-April 2016 and July 2019-March 2020 using iterated particle filtering. The model was used to simulate spread of cVDPV2 infection from July 2019 to explore impact of various proposed vaccination responses on stopping transmission and risk of spread of reverted Sabin-2 under varying assumptions of impacts from COVID-19 lockdown measures on movement patterns as well as declines in vaccination coverage. RESULTS: Simulated monthly incidence of cVDPV2 from the best-fit model demonstrated general spatio-temporal alignment with observed cVDPV2 cases. The model predicted substantial spread of cVDPV2 infection, with widespread transmission through 2020 in the absence of any vaccination activities. Vaccination responses were predicted to substantially reduce transmission and case burden, with a greater impact from earlier responses and those with larger geographic scope. While the greatest risk of seeding reverted Sabin-2 was predicted in areas targeted with OPV2, subsequent spread was greatest in areas with no or delayed response. The proposed vaccination strategy demonstrated ability to stop the cVDPV2 outbreak (with low risk of reverted Sabin-2 spread) by February 2021. CONCLUSION: Outbreak response vaccination campaigns against cVDPV2 will be challenging throughout the COVID-19 pandemic but must be implemented urgently when feasible to stop transmission of cVDPV2.

Quantifying movement patterns and vaccination status of high risk mobile populations in Pakistan and Afghanistan to inform poliovirus risk and vaccination strategy.

BACKGROUND: Stopping serotype 1 wild poliovirus transmission in Pakistan and Afghanistan requires ensuring all children <5 years of age are repeatedly vaccinated, including the large proportion living in mobile groups. Vaccinating children living in high-risk mobile populations (HRMPs) remains a priority for the polio programme. METHODS: In 2017-2018, group-level censuses were conducted in 43 districts of Pakistan, gathering information for all HRMP children <5 years of age residing in settlements. Demographic and mobility information was collected, including HRMP type, ethnicity, language, mode of transportation and movement patterns. Vaccination status was recorded for the most recent polio campaign. Proportion of HRMP children by demographic factors and mode of transportation was determined and the magnitude of movement was quantified based on the origin, previous and next locations. Magnitude of cross-border movement with Afghanistan was evaluated, as was primary crossing point. Vaccination status was evaluated for each district by demographic and mode of transportation information. RESULTS: In total, 188,130 HRMP children <5 years of age were assessed. The predominant HRMP type, ethnic group, language and mode of transport was Afghan refugees (27%), Pashtun (69%), Pashto (69%) and bus (52%). Overall, 84% of children originated outside of their current district, including 29% from Afghanistan. Previous and next locations, were reported outside of current location by 34% and 77% of children. Afghanistan was previous and next location for 5% and 11% of children, with 5.5% and 3% of children crossing the Afghanistan border in the past 6-months and next 3-months. Primary crossing route was Torkham (79%). Overall vaccination coverage was 98% (IQR: 96%-99%) and consistently >90% across HRMP type, ethnic group, language and mobility means. CONCLUSION: Large numbers of HRMPs were found across Pakistan, with substantial links throughout the country and with Afghanistan. While vaccination coverage of HRMPs was high, ensuring these populations are consistently vaccinated remains a priority.

Needle-free injectors for mass administration of fractional dose inactivated poliovirus vaccine in Karachi, Pakistan: A survey of caregiver and vaccinator acceptability.

The first large-scale vaccination campaign using needle-free jet injectors to administer fractional doses of inactivated poliovirus vaccine (fIPV) was conducted in Karachi, Pakistan, in February 2019. Data on acceptability of jet injectors were collected from 610 vaccinators and 4898 caregivers during the first four days of the campaign. Of those with prior needle and syringe experience, both vaccinators and caregivers expressed a strong preference for jet injectors (578/592 [97.6%] and 4792/4813 [99.6%], respectively), citing ease of use, appearance, and child's response to vaccination. Among caregivers, 4638 (94.7%) stated they would be more likely to bring their child for vaccination in a future campaign that used jet injectors. Mean vaccine coverage among towns administering fIPV was 98.7% - an increase by 18.4% over the preceding campaign involving full-dose IPV. Our findings demonstrate the strong acceptability of fIPV jet injectors and highlight the potential value of this method in future mass campaigns.