Oral Polio Vaccine Research Articles

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.

Prevalence of vaccine-derived poliovirus in sewage waters in Maiduguri, Borno State, Nigeria.

After a long global battle with wild poliovirus, the virus has been defeated through researches and vaccination using the oral polio vaccine and inactivated polio vaccine as well as sensitization. The issue that is now of global concern is that of vaccine-derived poliovirus which emerged from the unstable oral polio vaccine. Ninety sewage water samples were collected from slums in Maiduguri using grab method, concentrated using two phase separation method and subjected to intratypic differentiation and vaccine-derived poliovirus screening. The result revealed the presence of Sabin 1in 17 samples (61.0%) and Sabin 3 in 22 samples (79.0%), all of which were positive after vaccine-derived poliovirus screening. The presence of strains of Sabin 1 and Sabin 3 in the sewage water samples collected is an indication of virus shedding in individuals which could be as a result of vaccination or contact with the faeces infected or vaccinated individuals.

The impact of early-life access to oral polio vaccines on disability: evidence from India

The impact of early-life access to oral polio vaccines on disability: evidence from India

Improved vaccination coverage after two rounds of multi-antigenic catch-up vaccination in Mauritania.

Although Mauritania carried out its Expanded Programme on Immunization (EPI), in 2015 the goal of vaccination coverage (VC) remained unmet in Bassikounou district and Mbera camp, contexts with large migrant populations. In response, during 2018, the national authorities, together with Médecins Sans Frontières organised two rounds of multi-antigenic mass vaccination campaigns (2RMASVC). The campaigns included oral polio (OPV), pneumococcal (PCV13), pentavalent and rotavirus vaccines for all eligible children six weeks to 59 months old. This study describes the results of the 2RMASVC. Cross-sectional household VC surveys (VCS1 and VCS2) were conducted before and after the 2RMASVC. Data were collected on vaccination status according to self-reporting and vaccination cards, and on reasons for non-vaccination (RNV). In total, 4,569 children received at least one dose of vaccine in the first round and 5,602 children in the second. Baseline VC, as fully vaccinated, according to VCS1, was 59.9% of children 12 to 59 months in Bassikounou district and 65.8% in Mbera camp. After the 2RMASVC, the coverages increased to 84.7% and 75.9% respectively. Absence from home, lack of motivation, late initiation of vaccinations and lack of awareness about vaccination were the main RNV during the 2RMASVC. Although the 2RMASVC did not reach its goal of 90%-95% VC, the strategy significantly increased VC in the two settings for children aged 12 to 59 months. Therefore, this catch-up approach could be considered to improve VC of children who miss out of the EPI strategy in resource-limited settings.

Impact of COVID -19 on expanded programme on Immunisation in District Dir lower Khyber Pakhtunkhwa.

To study the impact of coronavirus disease-2019 on Expanded Programme on Immunisation in a rural setting. The descriptive, cross-sectional study was conducted in five union councils of District Dir Lower, in the Khyber Pakhtunkhwa province of Pakistan. Data was collected from March to August 2020, which was a period of lockdowns in the wake of the coronavirus disease-2019, and then from March to August 2021. The sample comprised children aged <2 years. Data was analysed using SPSS 25. Of the 330 children, 210(63.6%) were boys, and 120(36.4%) were girls, and all 330(100%) were located in rural areas. First-phase data showed that the maximum coverage rate of immunisation was 258(78.2%) noted in OPV1(Oral Polio Vaccine) Penta1(Pentavalent vaccine), PCV10-1 (Pneumococcal pneumonia) and Rota 1(Rota Vaccine), and the least vaccination rate was 68.2% for Measle-1. In the second phase, 23% incline was noted in Measles-2 vaccination, followed by 16.3% in OPV2, Penta 2, PCV10-2 and Rota 2, 16% in Measles-1, 14% in OPV-3, Penta-3, PCV10-3, Rota-3 and IPV, 11.5% in OPV-1, Penta-1, PCV10-1, and Rota-1, and 10.6% in OPV-0 and BCG-0. Immunisation programme was affected by lockdowns during the active phase of the coronavirus disease-2019 pandemic.

Can earlier BCG-Japan and OPV vaccination reduce early infant mortality? A cluster-randomised trial in Guinea-Bissau

ObjectiveTo assess the effect of providing BCG and oral polio vaccine (OPV) at an early home visit after delivery.DesignCluster-randomised trial, randomising 92 geographically defined clusters 1:1 to intervention/control arms.SettingBandim Health...

Tolerability, safety, and immunogenicity of the novel oral polio vaccine type 2 in children aged 6 weeks to 59 months in an outbreak response campaign in The Gambia: an observational cohort study

Novel oral polio vaccine type 2 (nOPV2) has been used to interrupt circulating vaccine-derived poliovirus type 2 outbreaks following its WHO emergency use listing. This study reports data on the safety and immunogenicity of nOPV2 over two rounds of a campaign in The Gambia. This observational cohort study collected baseline symptoms (vomiting, diarrhoea, irritability, reduced feeding, and reduced activity) and axillary temperature from children aged 6 weeks to 59 months in The Gambia before a series of two rounds of a nOPV2 campaign that took place on Nov 20-26, 2021, and March 19-22, 2022. Serum and stool samples were collected from a subset of the participants. The same symptoms were re-assessed during the week following each dose of nOPV2. Stool samples were collected on days 7 and 28, and serum was collected on day 28 following each dose. Adverse events, including adverse events of special interest, were documented for 28 days after each campaign round. Serum neutralising antibodies were measured by microneutralisation assay, and stool poliovirus excretion was measured by real-time RT-PCR. Of the 5635 children eligible for the study, 5504 (97·7%) received at least one dose of nOPV2. There was no increase in axillary temperature or in any of the baseline symptoms following either rounds of the campaigns. There were no adverse events of special interest and no other safety signals of concern. Poliovirus type 2 seroconversion rates were 70% (95% CI 62 to 78; 87 of 124 children) following one dose of nOPV2 and 91% (85 to 95; 113 of 124 children) following two doses. Poliovirus excretion on day 7 was lower after the second round (162 of 459 samples; 35·3%, 95% CI 31·1 to 39·8) than after the first round (292 of 658 samples; 44·4%, 40·6 to 48·2) of the campaign (difference -9·1%; 95% CI -14·8 to -3·3), showing the induction of mucosal immunity. In a campaign in west Africa, nOPV2 was well tolerated and safe. High rates of seroconversion and evidence of mucosal immunity support the licensure and WHO prequalification of this vaccine. Bill & Melinda Gates Foundation.

Immunisation coverage and factors associated with incomplete immunisation in children under two during the COVID-19 pandemic in Sierra Leone

BackgroundRoutine childhood immunisation is one of the most important life-saving public health interventions. However, many children still have inadequate access to these vaccines and millions remain (partially) unvaccinated globally. As the COVID-19 pandemic disrupted health systems worldwide, its effects on immunisation have become apparent. This study aimed to estimate routine immunisation coverage among children under two in Sierra Leone and to identify factors associated with incomplete immunisation during the COVID-19 pandemic.MethodsA cross-sectional household survey was conducted in three districts in Sierra Leone: Bombali, Tonkolili and Port Loko. A three-stage cluster sampling method was followed to enrol children aged 10–23 months. Information regarding immunisation status was based on vaccination cards or caretaker’s recall. Using WHO’s definition, a fully immunised child received one BCG dose, three oral polio vaccine doses, three pentavalent vaccine doses and one measles-containing vaccine dose. Following the national schedule, full immunisation status can be achieved at 9 months of age. Data were weighted to reflect the survey’s sampling design. Associations between incomplete immunisation and sociodemographic characteristics were assessed through multivariable logistic regression.ResultsA total of 720 children were enrolled between November and December 2021. Full vaccination coverage was estimated at 65.8% (95% CI 60.3%-71.0%). Coverage estimates were highest for vaccines administered at birth and decreased with doses administered subsequently. Adjusting for age, the lowest estimated coverage was 40.7% (95% CI 34.5%-47.2%) for the second dose of the measles-containing vaccine. Factors found to be associated with incomplete immunisation status were: living in Port Loko district (aOR = 3.47, 95% CI = 2.00-6.06; p-value < 0.001), the interviewed caretaker being Muslim (aOR = 1.94, 95% CI = 1.25–3.02; p-value = 0.015) and the interviewed caretaker being male (aOR = 1.93, 95% CI = 1.03–3.59, p-value = 0.039).ConclusionThough full immunisation coverage at district level improved compared with pre-pandemic district estimates from 2019, around one in three surveyed children had missed at least one basic routine vaccination and over half of eligible children had not received the recommended two doses of a measles-containing vaccine. These findings highlight the need to strengthen health systems to improve vaccination uptake in Sierra Leone, and to further explore barriers that may jeopardise equitable access to these life-saving interventions.

Factors associated with full childhood vaccination coverage among young mothers in Northern Nigeria.

wide regional variation in immunization coverage still persists in Nigeria. Full Immunization Coverage (FIC) for more than 80% of all states in the northern region is lower than 40% relative to their southern counterpart. Studies focusing on young women in the north remain sparse, despite the high prevalence of early marriage and poor health-seeking behavior. This study examines FIC among young women in northern Nigeria. we performed a secondary analysis of the 2013 and 2018 Nigeria Demographic and Health Survey on 1,198 women of children aged 12-23 months in 2013 and 405 in the 2018 dataset. Analysis was limited to young women 15-24 years, residing in Northern Nigeria. We used logistics regression to predict factors associated with FIC. the proportion of fully immunized children was low, at 11% in 2013 and 18% in 2018. The coverage for most vaccines was low, except for the oral polio vaccine. The children of mothers who had health card [(aOR=18.1,95% C.I (8.1-40.7)], in 2013 and 2018 [(aOR=12.7, 95% C.I (5.9-27.1)], attended ANC [(aOR=8.6, 95% C.I (2.4-30.9)] in 2013 and had facility delivery [(aOR=2.0, 95% C.I (1.0-4.1)] in 2018 were more likely to be fully immunized. the study found FIC among children of young women in Northern Nigeria was abysmally low. Ownership of health care, antenatal attendance, and facility delivery significantly predicted the odds of FIC. These findings suggest the need for approaches that remove barriers to good health-seeking behavior, especially among young mothers in Northern Nigeria.

Outbreak Response to Circulating Vaccine-Derived Poliovirus in Three Northern Regions of Ghana, 2019.

Background: Circulating Vaccine-Derived Poliovirus Type 2 (cVDPV2) was isolated in sewage and later in stool samples from children with acute flaccid paralysis (AFP) in northern Ghana. Method: A multidisciplinary and multisectoral team investigated this outbreak and reported on epidemiological and laboratory investigations. Sewage/wastewater samples were collected from the environment, while stool samples were collected from AFP/contact children under 5 years of age. The samples were processed for virus isolation, and positive isolates were sequenced. We also conducted a descriptive investigation involving a review of records, active case search, and Monovalent Oral Polio Vaccine 2 campaigns. Additionally, we interviewed caregivers about the vaccination status of their children, as well as their knowledge on polio prevention. Water quality, sanitation, hygiene practices, and health-seeking behaviours were also assessed. Results: A total of 18 cVDPV2 were confirmed in the three regions of Ghana during the outbreak in 2019-2020. All strains were genetically linked to a Nigerian cVDPV2 strain NIE-KWS-KSB-18-006HC29 that circulated in 2018. Evaluation of the surveillance system shows that officers have good knowledge of AFP and know how to collect samples, package them, and ship them to the laboratory. Few communities had access to potable water. Open defecation was common, and the water supply, sanitation, and hygiene practices of the communities were poor. Conclusion: The cVDPV2 outbreak represents the first time cVDPV2 has circulated in the country since Ghana embarked on the polio eradication program in 1996. However, with quality mOPV2 mop-up campaigns, a nationwide IPV catch-up campaign coupled with enhanced surveillance measures, transmission was interrupted.

Monitoring the evolution of vaccine-derived poliovirus in East and Southern African countries, 2010 - 2021.

the Africa region was certified indigenous wild poliovirus-free in August 2020. Countries in East and Southern Africa have, during acute flaccid paralysis (AFP) and environmental surveillance (ES), detected equally concerning vaccine-derived polioviruses (VDPVs) that have not been systematically documented to guide programming in the sub-region. The study documents trends and salient observations of the VDPVs by country of detection, for 11 years from 2010 to 2021. we conducted secondary data analysis, a descriptive study design, by deploying field and laboratory of AFP and environmental surveillance databases of the 20 East and Southern African countries from 2010 to 2021. a total of 318 VDPVs were reported over the study period. The majority were from AFP cases (58.8%) and the rest equally distributed between healthy community children and environmental surveillance sources. More polioviruses were detected after 2016 than during the period before. We observed that more boys were affected by VDPVs compared to girls. Children under 5 years were more affected than other age groups, with a mean age of 3.6 years. Delay of samples in the field seemed to increase the likelihood of not reporting VDPVs and not mounting timely public health detailed investigations and vaccination responses. the study provides useful evolutional trends of VDPVs for surveillance and vaccination programming. We also noted that the VDPV2s have been increasing after the 2016 tOPV to oral polio vaccine (bOPV) switch. The COVID-19 pandemic emergence in 2020, led to a decline in AFP, ES surveillance, and immunization activities. Our findings point to the need to implement enhanced tailored childhood immunization recovery strategies and to speed up the use of inactivated polio vaccine (IPV) to boost population immunity.

Adverse Events Following Immunization with Novel Oral Polio Vaccine Type 2, and the Experience and Challenges of Reporting in Sierra Leone [Response to Letter

Adverse Events Following Immunization with Novel Oral Polio Vaccine Type 2, and the Experience and Challenges of Reporting in Sierra Leone [Response to Letter

Oral polio vaccine stockpile modeling: insights from recent experience

ABSTRACTBackgroundAchieving polio eradication requires ensuring the delivery of sufficient supplies of the right vaccines to the right places at the right times. Despite large global markets, decades of use, and large quantity purchases of polio vaccines by national immunization programs and the Global Polio Eradication Initiative (GPEI), forecasting demand for the oral poliovirus vaccine (OPV) stockpile remains challenging.Research design and methodsWe review OPV stockpile experience compared to pre-2016 expectations, actual demand, and changes in GPEI policies related to the procurement and use of type 2 OPV vaccines. We use available population and immunization schedule data to explore polio vaccine market segmentation, and its role in polio vaccine demand forecasting.ResultsWe find that substantial challenges remain in forecasting polio vaccine needs, mainly due to (1) deviations in implementation of plans that formed the basis for earlier forecasts, (2) lack of alignment of tactics/objectives among GPEI partners and other key stakeholders, (3) financing, and (4) uncertainty about development and licensure timelines for new polio vaccines and their field performance characteristics.ConclusionsMismatches between supply and demand over time have led to negative consequences associated with both oversupply and undersupply, as well as excess costs and potentially preventable cases.

Novel oral polio vaccine for serotype 2: new hope

Novel oral polio vaccine for serotype 2: new hope

Geospatial Analyses of Recent Household Surveys to Assess Changes in the Distribution of Zero-Dose Children and Their Associated Factors before and during the COVID-19 Pandemic in Nigeria.

The persistence of geographic inequities in vaccination coverage often evidences the presence of zero-dose and missed communities and their vulnerabilities to vaccine-preventable diseases. These inequities were exacerbated in many places during the coronavirus disease 2019 (COVID-19) pandemic, due to severe disruptions to vaccination services. Understanding changes in zero-dose prevalence and its associated risk factors in the context of the COVID-19 pandemic is, therefore, critical to designing effective strategies to reach vulnerable populations. Using data from nationally representative household surveys conducted before the COVID-19 pandemic, in 2018, and during the pandemic, in 2021, in Nigeria, we fitted Bayesian geostatistical models to map the distribution of three vaccination coverage indicators: receipt of the first dose of diphtheria-tetanus-pertussis-containing vaccine (DTP1), the first dose of measles-containing vaccine (MCV1), and any of the four basic vaccines (bacilli Calmette-Guerin (BCG), oral polio vaccine (OPV0), DTP1, and MCV1), and the corresponding zero-dose estimates independently at a 1 × 1 km resolution and the district level during both time periods. We also explored changes in the factors associated with non-vaccination at the national and regional levels using multilevel logistic regression models. Our results revealed no increases in zero-dose prevalence due to the pandemic at the national level, although considerable increases were observed in a few districts. We found substantial subnational heterogeneities in vaccination coverage and zero-dose prevalence both before and during the pandemic, showing broadly similar patterns in both time periods. Areas with relatively higher zero-dose prevalence occurred mostly in the north and a few places in the south in both time periods. We also found consistent areas of low coverage and high zero-dose prevalence using all three zero-dose indicators, revealing the areas in greatest need. At the national level, risk factors related to socioeconomic/demographic status (e.g., maternal education), maternal access to and utilization of health services, and remoteness were strongly associated with the odds of being zero dose in both time periods, while those related to communication were mostly relevant before the pandemic. These associations were also supported at the regional level, but we additionally identified risk factors specific to zero-dose children in each region; for example, communication and cross-border migration in the northwest. Our findings can help guide tailored strategies to reduce zero-dose prevalence and boost coverage levels in Nigeria.

Effect of national immunisation campaigns with oral polio vaccine on all-cause mortality in children in rural northern Ghana: 20 years of demographic surveillance cohort data

Studies from Guinea-Bissau and Bangladesh have shown that campaigns with oral polio vaccine (C-OPV) may be associated with 25-31% lower child mortality. Between 1996 and 2015, Ghana had 50 national C-OPVs and numerous campaigns with vitamin A supplementation (VAS), and measles vaccine (MV). We investigated whether C-OPVs had beneficial non-specific effects (NSEs) on child survival in northern Ghana. We used data from a health and demographic surveillance system in the Navrongo Health Research Centre in rural northern Ghana to examine mortality from day 1-5 years of age. We used Cox models with age as underlying time scale to calculate hazard ratios (HR) for the time-varying covariate "after-campaign" mortality versus "before-campaign" mortality, adjusted for temporal change in mortality, other campaign interventions and stratified for season at risk. From 1996 to 2015, 75,610 children were followed for 280,156 person-years between day 1 and 5 years of age. In initial analysis, assuming a common effect across all ages, we did not find that OPV-only campaigns significantly reduced all-cause mortality, the HR being 0.96 (95% CI: 0.88-1.05). However, we subsequently found the HR differed strongly by age group, being 0.92 (0.75-1.13), 1.29 (1.10-1.51), 0.79 (0.66-0.94), 0.67 (0.53-0.86) and 1.03 (0.78-1.36) respectively for children aged 0-2, 3-5, 6-8, 9-11 and above 12 months of age (p<0.001). Triangulation of the evidence from this and previous studies suggested that increased frequency of C-OPVs and a different historical period could explain these results. In Ghana, C-OPVs had limited effects on overall child survival. However, triangulating the evidence suggested that NSEs of C-OPVs depend on age of first exposure and routine vaccination programs. C-OPVs had beneficial effects for children that were not exposed before 6 months of age. These non-specific effects of OPV should be exploited to further reduce child mortality. DANIDA; Else og Mogens Wedell Wedellsborgs Fond.

1744. Next generation sequencing (NGS) optimization of Oral Polio Vaccine samples

Abstract Background As wild poliovirus is eradicated, preventing circulation of vaccine-derived poliovirus is top priority. Our lab developed real-time multiplex PCR and deep sequencing methods to detect and characterize OPV strains directly from stool samples. This method requires gel purification of PCR product created from viral RNA in stool samples. However, gel purification causes significant genetic material loss and is time consuming. Here, we explore combinations of different purification and NGS methods to optimize sequencing. Methods 554 OPV positive samples from a previous study were used. 991 isolates were identified: 268 serotype 1 (S1), 405 serotype 2 (S2), and 318 serotype 3 (S3). PCR amplicons created from viral RNA in stool were run through a 0.08% agarose gel to identity presence of the ∼3.5kb amplicon of interest. Amplicons then underwent 1 of 4 purification methods (Table 1) with those yielding DNA &amp;gt;10ng/ul sequenced using 1 of 2 NGS techniques (Miseq vs Nextseq). Different Purification Methods Used Prior to NGS Results Gel purification: 42/126 (33.3%) S1 and 45/121(37.2%) S2 banded amplicons had a DNA concentration of &amp;gt;10ng/ul, as required for NGS. DNA purification: 449/450 (99.8%) S2 (259 banded) and all 318 (100%) S3 (170 banded) amplicons had concentrations &amp;gt;10ng/ul. S1 (n=145) samples had a higher mean coverage (MC) of 2850.02 than S2’s (n=208) MC of 792.56 and S3’s (n=217) MC of 256.78. Also, Nextseq (n=315) had a higher MC of 1486.78 than Miseq’s (n=255) MC of 648.99. Table 2 shows the MC for each purification and NGS method grouping and Graph 1 shows each grouping’s sample Ct value graphed against MC. 5/71 (7%) non-banded amplicons yielded sufficient sequencing coverage. There was a negative correlation between increasing Ct and coverage and a weak positive correlation between DNA concentration and coverage. Coverage of OPV Positive Samples by Purification and NGS Methods Ct Value Against Mean Coverage of Samples by Serotype and Purification and NGS Method Groups Conclusion DNA-purification methods (DPM) retain more DNA than gel-purification methods (GPM), therefore capturing a wider range of data. GPM may cause data loss and misrepresentation from reduction of sample size and variety, particularly of samples for within host variation analysis. However, the DNA retained via DPM were not OPV-specific, causing a need for a higher amplicon input volume to than GPM for the same coverage. DPM of band-producing samples with a Ct value of &amp;lt; 34 followed by Nextseq may be most optimal for NGS. Disclosures Yvonne A. Maldonado, MD, Pfizer: Grant/Research Support|Pfizer: Site Investigator, DSMB member

1637. Safety Evaluation of the Novel Oral Polio Vaccine Type 2 during a National Supplementary Immunisation Activity in Uganda, a Multipronged Approach: January–March 2022

Abstract Background Data from clinical trials show that novel oral poliovirus vaccine type 2 (nOPV2) is safe. However, nOPV2 is under emergency use listing, and continued vaccine safety monitoring is required to support licensure and World Health Organization (WHO) prequalification. In January 2022, Uganda introduced nOPV2 in a national supplementary immunization activity (SIA) in response to a circulating vaccine derived poliovirus outbreak, vaccinating 9.8 million children &amp;lt; 5 years old. We sought to identify and characterize safety events following nOPV2 vaccination Methods We evaluated the safety of nOPV2 following the SIA in Uganda using a multi-pronged approach: 1) routine passive surveillance for adverse events following immunization (AEFI), 2) active hospital-based surveillance for adverse events of special interest (AESI) 3) active acute flaccid paralysis (AFP) surveillance, and 4) active, cohort event monitoring (CEM) among a nationally representative sample of 2000 households in 200 enumeration areas for 42 days following administration of the nOPV2 vaccine. The national AEFI committee conducted causality assessment for all reported serious AEFI and pre-specified AESI conditions using global guidelines. Results During 14 January–11 March 2022, 1,157 adverse events were identified: 43 (3.7%) from passive surveillance, 5 (0.43%) from hospital-based surveillance, 157 (14%) from AFP surveillance, and 952 (82%) from CEM. The most commonly reported adverse events identified through CEM 0-3 days post-vaccination were fever (n=377, 40%), diarrhea (n=147, 15%), and malaise (n=107, 11%). Through all surveillance systems, 171 events underwent causality assessment. Among these 7 (4%) were classified as vaccine product-related reactions (1 acute disseminated encephalomyelitis, 1 encephalitis, 1 fever, 3 gastro-enteritis, and 1 painful lower limbs), 101 (59%) were classified as coincidental events, and 63 (37%) were downgraded. Conclusion The majority of identified serious AEFI were classified as coincidental events. No unexpected safety signals were identified among children &amp;lt; 5 years old during the nOPV2 SIA in Uganda. This evaluation provides critical data to contribute to the vaccine’s safety profile and informs recommendations for use, pre-qualification, and licensure. Disclosures All Authors: No reported disclosures

A circulating vaccine-derived poliovirus type 2 outbreak in a chronic conflict setting: a descriptive epidemiological study in South Sudan – 2020 to 2021

BackgroundIn this study, we describe the epidemiological profile of an outbreak of the circulating Vaccine Derived Polio Virus type 2 in South Sudan from 2020 to 2021.MethodWe conducted a retrospective descriptive epidemiological study using data from the national polio/AFP surveillance database, the outbreak investigation reports, and the vaccination coverage survey databases stored at the national level.ResultsBetween September 2020 and April 2021, 59 cases of the circulating virus were confirmed in the country, with 50 cases in 2020 and 9 cases in 2021. More cases were males (56%) under five (93%). The median age of the cases was 23.4 ± 11.9 months, ranging from 1 to 84 months. All states, with 28 out of the 80 counties, reported at least one case. Most of the cases (44, 75%) were reported from five states, namely Warrap (31%), Western Bahr el Ghazal (12%), Unity (12%), Central Equatoria (10%), and Jonglei (10%). Four counties accounted for 45.8% of the cases; these are Gogrial West with 12 (20%), Jur River with 5 (8.5%), Tonj North with 5 (8.5%), and Juba with 5 (8.5%) cases.The immunization history of the confirmed cases indicated that 14 (24%) of the affected children had never received any doses of oral polio or injectable vaccines either from routine or during supplemental immunization before the onset of paralysis, 17 (28.8%) had received 1 to 2 doses, while 28 (47.5%) had received 3 or more doses (Fig. 4). Two immunization campaigns and a mop-up were conducted with monovalent Oral Polio Vaccine type 2 in response to the outbreak, with administrative coverage of 91.1%, 99.1%, and 97% for the first, second, and mop-up rounds, respectively.ConclusionThe emergence of the circulating vaccine-derived poliovirus outbreak in South Sudan was due to low population immunity, highlighting the need to improve the country’s routine and polio immunization campaign coverage.

Improvement of the qmosRT-PCR Assay and Its Application for the Detection and Quantitation of the Three Serotypes of the Novel Oral Polio Vaccine in Stool Samples.

Recently, genetically stable novel OPVs (nOPV) were developed by modifying the genomes of Sabin viruses of conventional OPVs to reduce the risk of reversion to neurovirulence and therefore the risk of generating circulating vaccine-derived polioviruses. There is a need for specific and sensitive methods for the identification and quantification of nOPV viruses individually and in mixtures for clinical trials and potentially for manufacturing quality control and environmental surveillance. In this communication, we evaluated and improved the quantitative multiplex one-step reverse transcriptase polymerase chain reaction (qmosRT-PCR) assay for the identification and quantification of nOPV viruses in samples with different formulations and virus concentrations and in virus-spiked stool samples. The assay was able to specifically identify at least 1 log10 CCID50/mL of each serotype in the presence of the two other serotypes at high concentrations (6-7 log10 CCID50/mL) in the same sample. In addition, the lowest viral concentration that the assay was able to detect in stool samples was 17 CCID50/mL for nOPV1 and nOPV2 viruses and 6 CCID50/mL for nOPV3. We also found high correlation between the expected and observed (by qmosRT-PCR) concentrations of spiked viruses in stool samples for all three nOPV viruses, with R-squared values above 0.95. The analysis of samples collected from an nOPV2 clinical trial showed that 100% of poliovirus type 2 was detected and few samples showed the presence of type 1 and 3 residuals from previous vaccinations with bOPV (at least 4 weeks prior vaccination with nOPV2), confirming the high sensitivity of the method. The qmosRT-PCR was specific and sensitive for the simultaneous identification and quantification of all three nOPV viruses. It can be used as an identity test during the nOPV manufacturing process and in evaluation of virus excretion in nOPV clinical trials.