Trivalent Oral Poliovirus Vaccine Research Articles

Exploring the path to polio eradication: insights from consecutive seroprevalence surveys among Pakistani children.

After trivalent oral poliovirus vaccine (tOPV) cessation, Pakistan has maintained immunity to type 2 poliovirus by administering inactivated polio vaccine (IPV) in routine immunization, alongside monovalent OPV type 2 (mOPV2) and IPV in supplementary immunization activities (SIAs). This study assesses the change in poliovirus type 2 immunity after tOPV withdrawal and due to SIAs with mOPV2 and IPV among children aged 6-11 months. Three cross-sectional sequential serological surveys were conducted in 12 polio high-risk areas of Pakistan. 25 clusters from each geographical stratum were selected utilizing probability proportional to size. Seroprevalence of type 2 poliovirus was 49%, with significant variation observed among surveyed areas; <30% in Pishin, >80% in Killa Abdullah, Mardan & Swabi, and Rawalpindi. SIAs with IPV improved immunity from 38 to 57% in Karachi and 60 to 88% in Khyber. SIAs with IPV following mOPV2 improved immunity from 62 to 65% in Killa Abdullah, and combined mOPV2 and IPV SIAs in Pishin improved immunity from 28 to 89%. Results also reflected that immunity rates for serotypes 1 and 3 were consistently above 90% during all three phases and across all geographical areas. The study findings highlight the importance of implementing effective vaccination strategies to prevent the re-emergence of poliovirus. Moreover, the results provide crucial information for policymakers working toward achieving global polio eradication.

Immune persistence after different polio sequential immunization schedules in Chinese infants

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Outbreak management strategies for cocirculation of multiple poliovirus types.

Prior modeling studies showed that current outbreak management strategies are unlikely to stop outbreaks caused by type 1 wild polioviruses (WPV1) or circulating vaccine-derived polioviruses (cVDPVs) in many areas, and suggested increased risks of outbreaks with cocirculation of more than one type of poliovirus. The surge of type 2 poliovirus transmission that began in 2019 and continues to date, in conjunction with decreases in preventive supplemental immunization activities (SIAs) for poliovirus types 1 and 3, has led to the emergence of several countries with cocirculation of more than one type of poliovirus. Response to these emerging cocirculation events is theoretically straightforward, but the different formulations, types, and inventories of oral poliovirus vaccines (OPVs) available for outbreak response present challenging practical questions. In order to demonstrate the implications of using different vaccine options and outbreak campaign strategies, we applied a transmission model to a hypothetical population with conditions similar to populations currently experiencing outbreaks of cVDPVs of both types 1 and 2. Our results suggest prevention of the largest number of paralytic cases occurs when using (1) trivalent OPV (tOPV) (or coadministering OPV formulations for all three types) until one poliovirus outbreak type dies out, followed by (2) using a type-specific OPV until the remaining poliovirus outbreak type also dies out. Using tOPV first offers a lower overall expected cost, but this option may be limited by the willingness to expose populations to type 2 Sabin OPV strains. For strategies that use type 2 novel OPV (nOPV2) concurrently administered with bivalent OPV (bOPV, containing types 1 and 3 OPV) emerges as a leading option, but questions remain about feasibility, logistics, type-specific take rates, and coadministration costs.

Assessing country compliance with circulating vaccine-derived poliovirus type 2 outbreak response standard operating procedures: April 2016 to December 2020.

Trivalent oral poliovirus vaccine (tOPV) was globally replaced with bivalent oral poliovirus vaccine (bOPV) in April 2016 ("the switch"). Many outbreaks of paralytic poliomyelitis associated with type 2 circulating vaccine-derived poliovirus (cVDPV2) have been reported since this time. The Global Polio Eradication Initiative (GPEI) developed standard operating procedures (SOPs) to guide countries experiencing cVDPV2 outbreaks to implement timely and effective outbreak response (OBR). To assess the possible role of compliance with SOPs in successfully stopping cVDPV2 outbreaks, we analyzed data on critical timelines in the OBR process. Data were collected on all cVDPV2 outbreaks detected for the period April 1, 2016 and December 31, 2020 and all outbreak responses to those outbreaks between April 1, 2016 and December 31, 2021. We conducted secondary data analysis using the GPEI Polio Information System database, records from the U.S. Centers for Disease Control and Prevention Polio Laboratory, and meeting minutes of the monovalent OPV2 (mOPV2) Advisory Group. Date of notification of circulating virus was defined as Day 0 for this analysis. Extracted process variables were compared with indicators in the GPEI SOP version 3.1. One hundred and eleven cVDPV2 outbreaks resulting from 67 distinct cVDPV2 emergences were reported during April 1, 2016-December 31, 2020, affecting 34 countries across four World Health Organization Regions. Out of 65 OBRs with the first large-scale campaign (R1) conducted after Day 0, only 12 (18.5%) R1s were conducted by the target of 28days after Day 0. Of the 89 OBRs with the second large-scale campaign (R2) conducted after Day 0, 30 (33.7%) R2s were conducted by the target of 56days after Day 0. Twenty-three (31.9%) of the 72 outbreaks with isolates dated after Day 0 were stopped within the 120-day target. Since "the switch", delays in OBR implementation were evident in many countries, which may be related to the persistence of cVDPV2 outbreaks >120days. To achieve timely and effective response, countries should follow GPEI OBR guidelines.

Analysis of population immunity to poliovirus following cessation of trivalent oral polio vaccine.

The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2). We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016. We account for the changes in routine immunization schedules and varying implementation of preventive and outbreak response SIAs, assuming homogenous coverages of 50% and 80% for SIAs. In areas with strong routine immunization, the switch from tOPV to bOPV has likely resulted in gains in population immunity to types 1 and 3 poliovirus. However, we estimate that improved immunogenicity of new schedules has not compensated for declines in preventive SIAs in areas with weak routine immunization. For type 2 poliovirus, without tOPV in routine immunization or SIAs, mucosal immunity has declined nearly everywhere, while use of mOPV2 has created highly heterogeneous population immunity for which it is important to take into account when responding to cVDPV2 outbreaks. The withdrawal of tOPV and declining allocations of resources for preventive bOPV SIAs have resulted in reduced immunity in vulnerable areas to types 1 and 3 poliovirus and generally reduced immunity to type 2 poliovirus in the regions studied, assuming homogeneous coverages of 50% and 80% for SIAs. The very low mucosal immunity to type 2 poliovirus generates substantially greater risk for further spread of cVDPV2 outbreaks. Emerging gaps in immunity to all serotypes will require judicious targeting of limited resources to the most vulnerable populations by the Global Polio Eradication Initiative (GPEI).

Response to back-to-back outbreaks of circulating vaccine-derived poliovirus type 2 in two nomadic pastoralist settlements in Oti Region, Ghana-2019

BackgroundThe global switch from trivalent oral poliovirus vaccine (OPV) to bivalent OPV in April 2016 without corresponding co-administration of inactivated poliovirus vaccine (IPV) until June 2018, created a cohort of poliovirus type 2 naïve children with risk of developing vaccine-derived poliovirus type 2 (VDPV2). In November and December 2019, two cases of circulating vaccine-derived poliovirus type 2 (cVDPV2) were confirmed in quick succession through Acute Flaccid Paralysis (AFP) surveillance in two nomadic pastoralist settlements in Oti Region. We investigated to determine the outbreak extent, identify risk factors and implement control and preventive measures.MethodsWe interviewed case-patients’ families, abstracted immunization records, assessed AFP surveillance and conducted rapid OPV and IPV vaccination coverage surveys. Using AFP case definition of any child less than 15 years in the community with sudden onset of paralysis from July to November 2019 (in case-patient 1’s district) and August to December 2019 (in case-patient 2’s district), we conducted active case search. Stool samples from apparently healthy children and close contacts of the case-patients were collected and tested for poliovirus. We conducted environmental assessment of the community to identify potential risk factors.ResultsCase-patient 1 was an eight-year-old female who had taken two doses of OPV while case-patient 2 was an eight-month-old male who had taken three out of required four OPV doses in addition to IPV at seven months. Families of both case-patients had either travelled to or received visitors from areas with confirmed cVDPV2. Of all children surveyed, eight (29.6%) of 27 and three (18.8%) of 16 eligible children in communities of case-patient 1 and 2 respectively had received required four doses of OPV. No AFP case was found in both communities and surrounding settlements. Both communities had no source of potable water and toilet facilities. A stool sample from a contact of case-patient 1 tested positive for cVDPV2.ConclusionOutbreaks of cVDPV2 occurred in insanitary, under-vaccinated nomadic pastoralist settlements in Oti Region. Three rounds of monovalent OPV vaccination campaigns for children under 5 years of age in the districts and region as well as countrywide IPV vaccination campaign for poliovirus type 2 naïve cohort were conducted.

Seroprevalence of poliovirus antibodies in Nigeria: refining strategies to sustain the eradication effort.

in 2016, a switch from trivalent oral poliovirus vaccine (OPV) (containing serotypes 1,2,3) to bivalent OPV (types 1,3) was implemented globally. We assessed the seroprevalence of poliovirus antibody levels in selected Nigerian states, before and after the switch, documented poliovirus type2 outbreak responses conducted and ascertained factors associated with immunity gaps based on seroprevalence rates. we conducted a secondary analysis of stored serum samples from the 2018 Nigeria National HIV/AIDS Indicator and Impact Survey. Serum from 1,185 children aged 0-119 months residing in one southern and four northern states were tested for serotype-specific PV neutralizing antibodies; seropositivity was a reciprocal titer ≥8. We conducted regression analysis to determine sociodemographic risk factors associated with low seroprevalence using SAS 9.4. children aged 24-119 months (pre-switch cohort) had seroprevalence against PV1, PV2, and PV3, of 97.3% (95% CI:96.4-98.2), 93.8% (95% CI:92.2-95.5), and 91.3% (95% CI:89.2-93.4), while children aged <24 months (post-switch) had seroprevalence of 86.0% (95% CI:81.2-90.8), 55.6% (95% CI: 47.7-63.4), and 77.2% (95% CI:71.0-83.4) respectively. Regression analysis showed age <24 months was associated with lower seroprevalence against all PV serotypes, (p<0.0001); females had lower seroprevalence against PV1 (p=0.0184) and PV2 (p=0.0354); northern states lower seroprevalence against PV1 (p=0.0039), while well-water source lower seroprevalence against PV3 (p=0.0288). this study showed high seroprevalence rates against PV 1, 2, and 3 in pre-switch children (aged 24-119 months). However, post-switch children (<24 months) had low immunity against PV2 despite outbreak responses. Strategies to increase routine immunization coverage and high-quality polio campaigns can increase immunity against polio virus.

One Full or Two Fractional Doses of Inactivated Poliovirus Vaccine for Catch-up Vaccination in Older Infants: A Randomized Clinical Trial in Bangladesh.

BackgroundThe polio eradication endgame called for the removal of trivalent oral poliovirus vaccine (OPV) and introduction of bivalent (types 1 and 3) OPV and inactivated poliovirus vaccine (IPV). However, supply shortages have delayed IPV administration to tens of millions of infants, and immunogenicity data are currently lacking to guide catch-up vaccination policies.MethodsWe conducted an open-label randomized clinical trial assessing 2 interventions, full or fractional-dose IPV (fIPV, one-fifth of IPV), administered at age 9–13 months with a second dose given 2 months later. Serum was collected at days 0, 60, 67, and 90 to assess seroconversion, priming, and antibody titer. None received IPV or poliovirus type 2-containing vaccines before enrolment.ResultsA single fIPV dose at age 9–13 months yielded 75% (95% confidence interval [CI], 6%–82%) seroconversion against type 2, whereas 2 fIPV doses resulted in 100% seroconversion compared with 94% (95% CI, 89%–97%) after a single full dose (P < .001). Two doses of IPV resulted in 100% seroconversion.ConclusionsOur study confirmed increased IPV immunogenicity when administered at an older age, likely due to reduced interference from maternally derived antibodies. Either 1 full dose of IPV or 2 doses of fIPV could be used to vaccinate missed cohorts, 2 fIPV doses being antigen sparing and more immunogenic.Clinical Trial RegistrationNCT03890497.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2020-June 2021.

As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from trivalent OPV (tOPV; containing Sabin strain types 1, 2, and 3) to bivalent OPV (bOPV; containing Sabin strain types 1 and 3) subsequent to the certified eradication of wild type poliovirus (WPV) type 2 in 2015 (1-3). Circulating vaccine-derived poliovirus (cVDPV) outbreaks* occur when transmission of Sabin strain poliovirus is prolonged in underimmunized populations, allowing viral genetic reversion to neurovirulence, resulting in cases of paralytic polio (1-3). Since the switch, monovalent OPV type 2 (mOPV2, containing Sabin strain type 2) has been used for response to cVDPV type 2 (cVDPV2) outbreaks; tOPV is used if cVDPV2 co-circulates with WPV type 1, and bOPV is used for cVDPV type 1 (cVDPV1) or type 3 (cVDPV3) outbreaks (1-4). In November 2020, the World Health Organization (WHO) Emergency Use Listing procedure authorized limited use of type 2 novel OPV (nOPV2), a vaccine modified to be more genetically stable than the Sabin strain, for cVDPV2 outbreak response (3,5). In October 2021, the Strategic Advisory Group of Experts on Immunization (WHO's principal advisory group) permitted wider use of nOPV2; however, current nOPV2 supply is limited (6). This report updates that of July 2019-February 2020 to describe global cVDPV outbreaks during January 2020-June 2021 (as of November 9, 2021)† (3). During this period, there were 44 cVDPV outbreaks of the three serotypes affecting 37 countries. The number of cVDPV2 cases increased from 366 in 2019 to 1,078 in 2020 (7). A goal of the Global Polio Eradication Initiative's (GPEI) 2022-2026 Strategic Plan is to better address the challenges to early CVDPV2 outbreak detection and initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission by the end of 2023 (8).

Immunogenicity of Fractional Dose Inactivated Poliovirus Vaccine in India.

IntroductionFollowing the withdrawal of Sabin type 2 from trivalent oral poliovirus vaccine (tOPV) in 2016, the introduction of ≥1 dose of inactivated poliovirus vaccine (IPV) in routine immunization was recommended, either as 1 full dose (0.5mL, intramuscular) or 2 fractional doses of IPV (fIPV—0.1mL, intradermal). India opted for fIPV. We conducted a comparative assessment of IPV and fIPV.MethodsThis was a 4-arm, open-label, multicenter, randomized controlled trial. Infants were enrolled and vaccines administered according to the study design, and the blood was drawn at age 6, 14, and 18 weeks for neutralization testing against all 3 poliovirus types.ResultsStudy enrolled 799 infants. The seroconversion against type 2 poliovirus with 2 fIPV doses was 85.8% (95% confidence interval [CI]: 80.1%-90.0%) when administered at age 6 and 14 weeks, 77.0% (95% CI: 70.5-82.5) when given at age 10 and 14 weeks, compared to 67.9% (95% CI: 60.4-74.6) following 1 full-dose IPV at age 14 weeks.ConclusionThe study demonstrated the superiority of 2 fIPV doses over 1 full-dose IPV in India. Doses of fIPV given at 6 and 14 weeks were more immunogenic than those given at 10 and 14 weeks. Clinical Trial Registry of India (CTRI). Clinical trial registration number was CTRI/2017/02/007793.

Circulation of Type 2 Vaccine-Derived Poliovirus in China in 2018-2019.

BackgroundChina implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) on May 1, 2016. During April 2018 to May 2019, the first outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV2) after the switch occurred in Xinjiang and Sichuan, China. Methods. We performed sequence analysis of VP1 and the whole genome to determine the genomic characteristics of type 2 cVDPVs, and carried out coverage surveys to assess the risk of viral propagation. Surveillance for environment and acute flaccid paralysis was intensified to enhance case ascertainment. Results. Comparison of the complete genomes between early (Xinjiang strain) and late strains (Sichuan strains) revealed that recombination pattern and reverse mutation of attenuation sites had been fixed early, but the mutations of the neutralizing antigenic sites were introduced over the circulation. The Markov Chain Monte Carlo tree showed that the cVDPV2 initial infection was April 2016, earlier than the switch. So, we speculated that the cVDPV2 was originated from tOPV recipients and spread among children with a low level of immunity against the type 2.ConclusionsThe detection of this outbreak combined acute flaccid paralysis (AFP) surveillance with environmental surveillance (ES) indicates that ES should be expanded geographically to further complement AFP surveillance.

Risk factors for the spread of vaccine-derived type 2 polioviruses after global withdrawal of trivalent oral poliovirus vaccine and the effects of outbreak responses with monovalent vaccine: a retrospective analysis of surveillance data for 51 countries in Africa

SummaryBackgroundExpanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in 2016 are delaying global polio eradication. We aimed to assess the effect of outbreak response campaigns with monovalent type 2 OPV (mOPV2) and the addition of inactivated poliovirus vaccine (IPV) to routine immunisation.MethodsWe used vaccination history data from children under 5 years old with non-polio acute flaccid paralysis from a routine surveillance database (the Polio Information System) and setting-specific OPV immunogenicity data from the literature to estimate OPV-induced and IPV-induced population immunity against type 2 poliomyelitis between Jan 1, 2015, and June 30, 2020, for 51 countries in Africa. We investigated risk factors for reported cVDPV2 poliomyelitis including population immunity, outbreak response activities, and correlates of poliovirus transmission using logistic regression. We used the model to estimate cVDPV2 risk for each 6-month period between Jan 1, 2016, and June 30, 2020, with different numbers of mOPV2 campaigns and compared the timing and location of actual mOPV2 campaigns and the number of mOPV2 campaigns required to reduce cVDPV2 risk to low levels.FindingsType 2 OPV immunity among children under 5 years declined from a median of 87% (IQR 81–93) in January–June, 2016 to 14% (9–37) in January–June, 2020. Type 2 immunity from IPV among children under 5 years increased from 3% (<1–6%) in January–June, 2016 to 35% (24–47) in January–June, 2020. The probability of cVDPV2 poliomyelitis among children under 5 years was negatively correlated with OPV-induced and IPV-induced immunity and mOPV2 campaigns (adjusted odds ratio: OPV 0·68 [95% CrI 0·60−0·76], IPV 0·82 [0·68−0·99] per 10% absolute increase in estimated population immunity, mOPV2 0·30 [0·20−0·44] per campaign). Vaccination campaigns in response to cVDPV2 outbreaks have been smaller and slower than our model shows would be necessary to reduce risk to low levels, covering only 11% of children under 5 years who are predicted to be at risk within 6 months and only 56% within 12 months.InterpretationOur findings suggest that as mucosal immunity declines, larger or faster responses with vaccination campaigns using type 2-containing OPV will be required to stop cVDPV2 transmission. IPV-induced immunity also has an important role in reducing the burden of cVDPV2 poliomyelitis in Africa.FundingBill & Melinda Gates Foundation, Medical Research Council Centre for Global Infectious Disease Analysis, and WHO.TranslationFor the French translation of the abstract see Supplementary Materials section.

Immunization Against Poliomyelitis and the Challenges to Worldwide Poliomyelitis Eradication.

Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed countries despite possessing different vaccine properties. Due to cost, ease of use, and other properties, the Expanded Programme on Immunization added OPV to the routine infant immunization schedule for low-income countries in 1974, but variable vaccine uptake and impaired immune responses due to poor sanitation limited the impact. Following launch of the Global Polio Eradication Initiative in 1988, poliomyelitis incidence has been reduced by >99% and types 2 and 3 wild polioviruses are now eradicated, but progress against type 1 polioviruses which are now confined to Afghanistan and Pakistan has slowed due to insecurity, poor access, and other problems. A strategic, globally coordinated replacement of trivalent OPV with bivalent 1, 3 OPV in 2016 reduced the incidence of vaccine-associated paralytic poliomyelitis (VAPP) but allowed the escape of type 2 vaccine–derived polioviruses (VDPV2) in areas with low immunization rates and use of monovalent OPV2 in response seeded new VDPV2 outbreaks and reestablishment of type 2 endemicity. A novel, more genetically stable type 2 OPV vaccine is undergoing clinical evaluation and may soon be deployed prevent or reduce VDPV2 emergences.

Estimation of oral poliovirus vaccine effectiveness in Afghanistan, 2010–2020

BackgroundAfghanistan is one of two countries with endemic wild poliovirus type 1 (WPV1). The oral poliovirus vaccine (OPV) is the predominant vaccine used for polio eradication. Although OPV has been administered in routine childhood immunization and during frequent supplementary immunization activities, WPV1 continues to circulate in Afghanistan and case incidence has been increasing since 2017. We estimated the effectiveness of OPV in Afghanistan during 2010–2020. MethodsWe conducted a matched case-control analysis using acute flaccid paralysis (AFP) surveillance data from 29,370 children < 15 years with AFP onset between January 1, 2010 and December 31, 2020. We matched children with confirmed WPV1 (cases) with children with non-polio AFP (controls) by age at onset of paralysis (+/- 3 months), date of onset of paralysis (+/- 3 months), and province of residence, and compared their reported OPV vaccination history to estimate the effectiveness of OPV in preventing paralysis by WPV1 using conditional logistic regression. To account for changes in OPV formulations provided over the analysis period, we stratified the analysis based on dates of the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) in April 2016. ResultsBetween January 1, 2010 and December 31, 2020, there were 329 WPV1 cases in Afghanistan. The per-dose estimated effectiveness of OPV against WPV1 was 19% (95% CI: 15%–22%) and of ≥ 7 doses was 94% (95% CI: 90%-97%). Before the global switch from tOPV to bOPV, the per-dose estimated effectiveness of OPV was 14% (95% CI: 11%-18%) and of ≥ 7 doses was 92% (95% CI: 85%-96%). After the switch, the per-dose estimated effectiveness of OPV against WPV1 was 32% (24%-39%) and of ≥ 7 doses was 96% (95% CI: 90%-99%). DiscussionOPV is highly effective in preventing paralysis by WPV1; these results indicate that continued WPV1 transmission in Afghanistan is due to failure to vaccinate, not failure of the vaccine. Although difficult to implement in parts of country, improving the administration of OPV in routine immunization and supplementary immunization activities will be critical for achieving polio eradication in Afghanistan.

Serotype 2 oral poliovirus vaccine (OPV2) choices and the consequences of delaying outbreak response.

The Global Polio Eradication Initiative (GPEI) faces substantial challenges with managing outbreaks of serotype 2 circulating vaccine-derived polioviruses (cVDPV2s) in 2021. A full five years after the globally coordinated removal of serotype 2 oral poliovirus vaccine (OPV2) from trivalent oral poliovirus vaccine (tOPV) for use in national immunization programs, cVDPV2s did not die out. Since OPV2 cessation, responses to outbreaks caused by cVDPV2s mainly used serotype 2 monovalent OPV (mOPV2) from a stockpile. A novel vaccine developed from a genetically stabilized OPV2 strain (nOPV2) promises to potentially facilitate outbreak response with lower prospective risks, although its availability and properties in the field remain uncertain. Using an established global poliovirus transmission model and building on a related analysis that characterized the impacts of disruptions in GPEI activities caused by the COVID-19 pandemic, we explore the implications of trade-offs associated with delaying outbreak response to avoid using mOPV2 by waiting for nOPV2 availability (or equivalently, delayed responses waiting for national validation of meeting the criteria for nOPV2 initial use). Consistent with prior modeling, responding as quickly as possible with available mOPV2 promises to reduce the expected burden of disease in the outbreak population and to reduce the chances for the outbreak virus to spread to other areas. Delaying cVDPV2 outbreak response (e.g., modeled as no response January-June 2021) to wait for nOPV2 can considerably increase the total expected cases (e.g., by as many as 1,300 cVDPV2 cases in the African region during 2021-2023) and increases the likelihood of triggering the need to restart widescale preventive use of an OPV2-containing vaccine in national immunization programs that use OPV. Countries should respond to any cVDPV2 outbreaks quickly with rounds that achieve high coverage using any available OPV2, and plan to use nOPV2, if needed, once it becomes widely available based on evidence that it is as effective but safer in populations than mOPV2.

Fractional-dose IPV in polio eradication

The development of fractional-dose inactivated poliovirus vaccine (fIPV) has been crucial to the global polio eradication initiative (GPEI) in the past decade, providing a dose-stretching and affordable option to enable global inactivated poliovirus vaccine (IPV) introduction. In April, 2016, the type 2 component of oral poliovirus vaccine (OPV) was withdrawn from routine immunisation because of the risk of vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the trivalent OPV was replaced with a bivalent form.

Updated Characterization of Poliovirus Transmission in Pakistan and Afghanistan and the Impacts of Different Outbreak Response Vaccine Options.

BackgroundPakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the COVID-19 pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed.MethodsWe updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (i.e., population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs).ResultsThe modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality.ConclusionsUsing trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV (mOPV2) offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas.

Post hoc analysis of two clinical trials to compare the immunogenicity and safety of different polio immunization schedules in Chinese infants.

BackgroundA comparative analysis of the immunogenicity and safety of different poliovirus immunization schedules in Chinese infants is imperative to guide the administration of efficient strategies for the eradication of poliomyelitis.MethodsA post hoc analysis was conducted with the data from two poliovirus vaccine clinical trials involving a combined total of 2,400 infants aged 60–90 days. Trivalent oral poliovirus vaccine (tOPV), bivalent oral poliovirus vaccine (bOPV), Sabin strain-based inactivated poliovirus vaccine (sIPV), and conventional inactivated poliovirus vaccine (cIPV) were used in different schedules, the immunogenicity and safety of which were compared 28 days after the last of three doses.ResultsIn a per-protocol set analysis, the tOPV-tOPV-tOPV schedule induced seroconversion in 99.1%, 98.2%, and 96.0% of the inoculated infants for poliovirus type I, II, and III, respectively. The seroconversions for poliovirus types I and III were each almost 100% after immunization with the cIPV-bOPV-bOPV, sIPV-sIPV-bOPV, cIPV-cIPV-bOPV, sIPV-sIPV-tOPV, cIPV-cIPV-tOPV, or sIPV-bOPV-bOPV schedule. However, the schedules that used one IPV dose followed by two (poliovirus type I and III) bOPV doses failed to induce high-level immunity against type II poliovirus. IPV-related schedules were associated with a slightly higher incidence of adverse events (AEs).ConclusionsIf the capacity of IPV can be increased, two or more doses of IPV should be administered before vaccination with bOPV in a sequential schedule to improve immunity against type II poliovirus.

Surveillance of immunization effectiveness and titer of type Ⅰ and type Ⅲ polio vaccine in Beijing before and after the adjustment of immunization strategy in 2012-2018

Objective: To analyze the changing trend of polio vaccine immunization effectiveness and vaccine titer in Beijing in 2012, 2014, 2016 and 2018 before and after the adjustment of polio vaccine immunization program strategy. Methods: According to the convenient sampling method,the vaccination clinics of Chaoyang and Yanqing Districts in 2012, Fengtai and Daxing Districts in 2014, Tongzhou and Pinggu Districts in 2016, Dongcheng and Shunyi Districts in 2018 were selected as monitoring points. A total of 292 children were selected 4-8 weeks after the completion of 3 doses polio vaccine basic immunization which were 3 doses of trivalent oral poliovirus vaccine（tOPV）schedule before the strategy adjustment in 2012-2014 and 1 dose of inactivated poliovirus vaccine (IPV) following 2 doses of bivalent oral poliovirus vaccine (bOPV) sequential schedule after the adjustment in 2016-2018. About 1.0 ml blood samples were collected to detect type Ⅰ and Ⅲ neutralizing poliovirus antibody. A total of 9 oral poliovirus vaccines (8 vaccines in 2012) were selected from different sources of vaccine storage every year to test the vaccine titer using random number method. Results: The [M（P25，P75）] age of 292 children was 5 (5, 6) months, and the ratio of male to female was 1.04 (149/143). In 2012, 2014, 2016 and 2018, 66,72,68 and 86 children were investigated respectively. After basic immunization, antibody positive rates for type Ⅰ and Ⅲ poliovirus were 100%, except 98.61% (71) for type Ⅰ poliovirus in 2014. The neutralizing antibody titer of type Ⅰ and Ⅲ poliovirus was higher in 2016 and 2018 than that in 2012 and 2014 (P<0.001). The average titer of tOPV were (6.05±0.15) and (6.16±0.12) lgCCID50 per dose in 2012 and 2014. The average titer of bOPV were (6.88±0.21) and (6.26±0.14) lgCCID50 per 100 μl in 2016 and 2018 (P<0.001). Conclusion: Before and after the adjustment of polio vaccine immunization strategy in Beijing, the basic immunization success rate of the IPV-bOPV sequential immunization schedule was good as well as full tOPV schedule. The level of polio antibody produced by the IPV-bOPV sequential immunization schedule was higher. After adjustment, bOPV titer in 2016 was significantly higher than those before adjustment, while bOPV titer decreased significantly in 2018.

Updated Characterization of Post-OPV Cessation Risks: Lessons from 2019 Serotype 2 Outbreaks and Implications for the Probability of OPV Restart.

After the globally coordinated cessation of any serotype of oral poliovirus vaccine (OPV), some risks remain from undetected, existing homotypic OPV-related transmission and/or restarting transmission due to several possible reintroduction risks. The Global Polio Eradication Initiative (GPEI) coordinated global cessation of serotype 2-containing OPV (OPV2) in 2016. Following OPV2 cessation, the GPEI and countries implemented activities to withdraw all the remaining trivalent OPV, which contains all three poliovirus serotypes (i.e., 1, 2, and 3), from the supply chain and replace it with bivalent OPV (containing only serotypes 1 and 3). However, as of early 2020, monovalent OPV2 use for outbreak response continues in many countries. In addition, outbreaks observed in 2019 demonstrated evidence of different types of risks than previously modeled. We briefly review the 2019 epidemiological experience with serotype 2 live poliovirus outbreaks and propose a new risk for unexpected OPV introduction for inclusion in global modeling of OPV cessation. Using an updated model of global poliovirus transmission and OPV evolution with and without consideration of this new risk, we explore the implications of the current global situation with respect to the likely need to restart preventive use of OPV2 in OPV-using countries. Simulation results without this new risk suggest OPV2 restart will likely need to occur (81% of 100 iterations) to manage the polio endgame based on the GPEI performance to date with existing vaccine tools, and with the new risk of unexpected OPV introduction the expected OPV2 restart probability increases to 89%. Contingency planning requires new OPV2 bulk production, including genetically stabilized OPV2 strains.