Search Results (46)

Neonatal defense against pathogens relies on maternal antibodies transferred both through the placenta (IgG) and through breast milk (primarily secretory IgA). Maternal IgG antibodies are transferred across the placenta to the fetus mainly via the neonatal Fc receptor (FcRn), which is expressed at high levels in placental syncytiotrophoblasts, and results in the acquisition of maternal-fetal IgG. Transplacental transfer via the FcRn pathway can provide therapeutic proteins and protective antibodies following maternal vaccination. However, maternal IgG antibodies can bind to vaccine antigens such as measles, tetanus, and poliovirus, resulting in rapid clearance through FcgRIIB-mediated inhibition and inadequate B cell activation. In this way, they can inhibit de novo immune responses and significantly reduce vaccine response. On the other hand, the interference that breast milk-derived antibodies may have on vaccine-induced immunity is still largely unknown. Vaccination against influenza, pertussis, and COVID-19 during pregnancy or lactation has been shown to induce the production of protective, pathogen-specific, secretory IgA and IgG antibodies in breast milk. Conversely, studies found that breast milk-derived antibodies of vaccinated mothers reduced vaccine-induced immunity in breastfed infants by accelerating the clearance of vaccine antigen, resulting in reduced antigen availability and reduced plasma cell formation after vaccination. Additional factors in middle- and low-income countries, including environmental (increased microbiome diversity, environmental intestinal dysfunction, malnutrition, co-infections) and breastfeeding practices, may exacerbate the interference effect of maternal antibodies. Current evidence supports that breastfeeding is associated with a reduced immunological response exclusively to the rotavirus vaccine. However, the limited evidence base to date precludes definitive conclusions regarding the role of breast milk-derived antibodies in modulating vaccine-induced immunity. Nevertheless, the evidence suggests that although maternal antibodies may theoretically reduce vaccine immunogenicity, the overall protective benefits of breastfeeding outweigh any potential interference with vaccine responses. Full article

Clusters of acute flaccid paralysis (AFP) caused by oral vaccine-derived poliovirus (VDPV) in 2022 and sporadic outbreaks in New York and Gaza highlight the ongoing risk of polio, alongside the persistent global threat posed by wild-type poliovirus. This study aims to develop and validate a quantitative reverse transcription PCR (RT-qPCR) panel that employs different primer–probe sets to simultaneously detect vaccine and wild-type poliovirus (WPV) in wastewater. Using an inactivated poliovirus vaccine (IPV) and engineered DNA fragments (eDNAf), the qPCR master mix (MM) performance, assay specificity, sensitivity (limit of detection, LOD), and recovery from IPV-spiked wastewater were evaluated. Compared with two-step RT-qPCR and qScript MM, one-step RT-qPCR with TaqMan MM improved sensitivity for the following polioviruses (PV): Sabin 1 in IPV and the eDNAf of Sabin 1, 2, and 3; WPV1 and WPV3; and poliovirus type 2 (any serotype 2). The LOD for Sabin 1 in IPV was 2.49 copies/PCR, while LODs for eDNAf of polio targets ranged from 1.06 to 3.12 copies/PCR. Sabin 1 recovery from IPV-spiked wastewater ranged from 10.26% to 57.27%. The RT-qPCR panel for poliovirus exhibited good specificity and sensitivity, with moderate viral recovery, enabling rapid implementation of wastewater monitoring for PV as needed. Full article

The aim of this research is to formulate and analyze a modified $S{I}_{p}IVR$ mathematical model to study the transmission dynamics of poliovirus and assess the impact of vaccination on disease control. The proposed model extends classical SEIV-type frameworks by incorporating a recovered compartment with long-term immunity and by replacing the traditional exposed class with a pre-infectious compartment ($I_p$) that captures silent viral shedding during the incubation phase of poliovirus. This modification addresses the critical epidemiological feature that individuals can transmit the virus before showing symptoms while maintaining biological accuracy in compartment definition. Several fundamental analytical properties are rigorously established, including positivity, boundedness, and the existence of a biologically meaningful invariant region. The basic reproduction number $R_0$ is derived using the next-generation matrix approach, and comprehensive stability analysis is carried out. The analysis shows that the DFE is locally and globally asymptotically stable whenever $R_0<1$. Using center manifold theory, a forward bifurcation is rigorously demonstrated, indicating that disease persistence emerges smoothly as $R_0$ crosses unity. Local and global sensitivity analyses of the basic reproduction number $R_0$ identify critical epidemiological parameters, and points to vaccination coverage and transmission rates as key drivers of outbreak dynamics. Numerical simulations confirm the analytical results and illustrates two different epidemiological scenarios, one with $R_0<1$, and another with $R_0>1$ along with neural network analysis by using the same data from both cases in a built-in function package in MATLAB-2020 software. It utilizes all of its hidden layers to check the data used by the model for validation performance and training and to find the absolute and mean squared errors. It also shows how vaccination suppresses the spread of infection. These findings provide a strong mathematical basis for public health policy, offering strategic insight into how vaccination campaigns might be optimized to accelerate progress toward global polio eradication. Full article

Poliovirus (PV), a historically significant enterovirus responsible for severe paralytic diseases, has seen its incidence dramatically reduced through widespread vaccination efforts, propelling global eradication initiatives. Despite the success of traditional oral poliovirus vaccines (OPVs) and inactivated poliovirus vaccines (IPVs), challenges such as vaccine-derived virus reversion and biosafety concerns during vaccine production persist. Virus-like particle (VLP) vaccines, which mimic native viral structures without containing viral genomes, offer enhanced safety profiles and robust immunogenicity, positioning them as promising candidates for next-generation poliovirus vaccines, especially in the post-certification era. This review systematically summarizes current progress in poliovirus VLP vaccine research, including the diverse expression systems employed for VLP production, strategies for peptide assembly and stabilization, and evaluations of antigenicity and immunogenicity. Additionally, it highlights structural analyses utilizing cutting-edge cryo-electron microscopy. By integrating recent developments in genetic engineering, structural biology, and immunology, this article discusses the advantages and challenges associated with poliovirus VLP vaccines and explores future directions aimed at supporting the global goal of a poliovirus-free world. This comprehensive overview aims to provide a theoretical foundation and technical guidance to facilitate the development and deployment of safer and more effective poliovirus vaccines. Full article

When the Global Polio Eradication Initiative (GPEI) began in 1988, the year 2000 target was clearly ambitious. Nonetheless, among 20 countries with endemic wild poliovirus transmission in 2000, only Afghanistan, Nigeria and Pakistan remained endemic in 2014; successful global eradication was anticipated within years. Transmission was interrupted in Nigeria after implementing innovative activities; unfortunately, transmission in Afghanistan and Pakistan has continued into 2025. An additional challenge has been controlling outbreaks and interrupting persistent transmission of circulating vaccine-derived poliovirus type 2 detected after global withdrawal of the use of Sabin strain type 2 oral poliovirus vaccine. The impediments to progress since 2014 are detailed and the challenges that the GPEI must successfully mitigate are reviewed herein. Primary challenges since the acute phase of the COVID-19 pandemic include the loss of a sense of urgency and political will/national ownership in stopping poliovirus transmission, lower childhood routine immunization coverage and the decreased quality of outbreak response campaigns. These facets need to be strengthened. Ongoing security challenges require continued vigilance in affected areas of wild poliovirus-endemic countries as well as in countries with persistent transmission of vaccine-derived poliovirus. Eradication can be achieved if the multiple challenges mentioned are urgently and more effectively mitigated. Decreased funding for the GPEI in 2025 represents the primary, acute challenge that, if not urgently addressed, may allow for the reversal of all progress to date. Full article

The detection of “silent” poliovirus (PV) circulation among clinically healthy populations is an important component of supplementary surveillance for poliomyelitis. Migrants from countries or regions where polio is endemic, affected by outbreaks, or at risk may contribute to the introduction of PVs of epidemic significance: wild poliovirus type 1, vaccine-derived polioviruses (VDPVs), or poliovirus type 2 into polio-free countries. Migrant children, refugees under 5 years of age, are considered a “risk group” in Russia and are subject to testing for PVs. During 2014–2023, guided by the algorithm of virological and molecular investigation of acute flaccid paralysis cases recommended by the WHO, 51,548 migrant children, arriving from 40 countries, were examined. Among 4% of children excreting various cytopathogenic viruses, polio excretors accounted for 20.8%. Among the PVs, PV3 was predominant (41.7%), and PV types 2, 1, and a mixture of PVs accounted for, respectively, 28.2%, 18.8%, and 11.3%. All isolates of PVs 1 and 3 were identified as Sabin-like. The detection of five children excreting epidemically significant PV2 (four VDPV2 and one Sabin-like) required an assessment of the risk of dissemination and additional immunization activities. Among 580 identified isolates of NPEV, the most abundant was the E. betacoxsakie species at 73.8% (CVB1–6, E11, E6, E13, E7). Information on NPEVs expands our knowledge of the spectrum of NPEVs circulating among healthy children worldwide, but its prognostic significance is still unclear. The detection of PVs in children from the “risk group” allows targeted anti-epidemic measures and is a significant advantage of this type of supplementary surveillance for polio. Full article

Background: Polio is an infectious viral disease that can cause paralytic complications and death. Despite global efforts to eradicate wild poliovirus, there are ongoing outbreaks globally and the mutated form of paralytic polio, i.e., circulating vaccine-derived poliovirus, is present in Nigeria. Low vaccination uptake and poor sanitation are responsible for outbreaks in countries where polio had previously been eliminated. This review identifies policies, strategies and interventions for polio eradication and assesses their impact on polio vaccine uptake and eradication efforts in Nigeria. Methods: A systematic literature review was conducted and guided by the Population, Intervention, Comparator and Outcome (PICO) framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart, with identified articles appraised using the Critical Appraisal Skills Program appraisal tool. Results: A total of 393 articles were identified, of which 26 articles were included. Key findings indicate polio intervention services, policies and mass campaigns have had a significant impact on eradicating WPV in Nigeria. However, there are gaps in variant polio eradication efforts, with low vaccination uptake, poor surveillance, vaccine hesitancy, lack of community engagement, weaknesses in the healthcare system and other challenges in Nigeria regionally and nationally, posing a risk to public health that threatens the eradication of all forms of polio in Nigeria. Conclusions: Recommendations are suggested for changes to practice and policy to improve polio vaccination uptake in Nigeria and globally in the short-term (1–2 years), mid-term (3–4 years) and long-term (5+ years). Collaborative targeted polio vaccination programs and funding of public health infrastructure are imperative globally alongside national strategic policy intervention frameworks to strengthen the World Health Organization Global Polio Eradication Initiative and improve vaccine uptake and monitoring of vaccine hesitancy. Simultaneous health-literate community engagement is needed to achieve and maintain polio eradication efforts, which must be integrated into national health frameworks and coordinated across the African continent. Full article

Background/Objectives: Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees and their contacts. A novel OPV2 vaccine (nOPV2) with enhanced genetic stability was developed recently; type 1 and type 3 nOPV strains were engineered using the nOPV2 genome as a backbone by replacing the capsid precursor polyprotein (P1) with that of Sabin strains type 1 and type 3, respectively. The nOPV vaccines have a high degree of sequence homology with the parental Sabin 2 genome, and some manufacturing facilities produce and store both Sabin OPV and nOPV. Therefore, detecting Sabin virus contaminations in nOPV lots is crucial. Methods: This study describes the development of pan quantitative reverse transcription polymerase chain reaction (panRT-PCR) and multiplex one-step RT-PCR (mosRT-PCR) assays for the straightforward detection and identification of contaminating Sabin viruses when present in significantly higher amounts of nOPV strains. Results: The two assays exhibit high specificity, reproducibility, and sensitivity to detect 0.0001% and 0.00001% of Sabin viruses in nOPV, respectively. Additionally, an analysis of 12 trivalent nOPV formulation lots using both methods confirmed that the nOPV lots were free from Sabin virus contamination. Conclusions: The results demonstrated that the RT-PCR assays are sensitive and specific. These assays are relevant for quality control and lot release of nOPV vaccines. Full article

Individuals with certain primary immunodeficiency disorders (PID) may be unable to clear poliovirus infection after exposure to oral poliovirus vaccine (OPV). Over time, vaccine-related strains can revert to immunodeficiency-associated vaccine-derived poliovirus (iVDPVs) that can cause paralysis in the patient and potentially spread in communities with low immunity. We reviewed the efforts for detection and management of PID patients with iVDPV infections and the epidemiology through an analysis of 184 cases reported to the World Health Organization (WHO) during 1962–2024 and a review of polio program and literature reports. Most iVDPV patients (79%) reported in the WHO Registry were residents in middle-income countries and almost half (48%) in the Eastern Mediterranean Region. Type 2 iVDPV was most frequently isolated (53%), but a sharp decline was observed after the switch to bivalent OPV in 2016, with only six cases reported during 2017–2024 compared to 63 during 2009–2016. Patients with common variable immunodeficiency have longer excretion of iVDPV than with other PID types. Implementation of sensitive sentinel surveillance to detect cases of iVDPV infection in high-risk countries and offer antiviral treatment to patients is challenged by competition with other health priorities and regulatory hurdles to the compassionate use of investigational antiviral drugs. Full article

The Global Polio Eradication Initiative (GPEI), launched in 1988, has successfully reduced wild poliovirus (WPV) cases by over 99.9%, with WPV type 2 and WPV3 declared eradicated in 2015 and 2019, respectively. However, as of 2024, WPV1 remains endemic in Afghanistan and Pakistan. Since 2000, outbreaks of circulating virus derived of polio vaccines (cVDPVs) have emerged in multiple regions, primary driven by low vaccine coverage rates (VCRs). The COVID-19 pandemic disrupted routine immunization, resulting in millions of unvaccinated children, and leaving many countries vulnerable to both WPV1 and cVDPVs outbreaks. This paper reviews the epidemiological landscape of poliomyelitis post the COVID-19 pandemic, and the strategies and challenges to achieve the global polio eradication. Full article

Background/Objectives: Although wild poliovirus type 2 has been eradicated, the prolonged transmission of the live- attenuated virus contained in the type-2 oral polio vaccine (OPV2) in under-immunized populations has led to the emergence of circulating vaccine-derived poliovirus type 2 (cVDPV2). The novel OPV2 (nOPV2) was designed to be more genetically stable and reduce the chance of cVDPV2 emergence while retaining comparable immunogenicity to the Sabin monovalent OPV2 (mOPV2). This study aimed to estimate the relative reduction in the emergence risk due to the use of nOPV2 instead of mOPV2. Methods: Data on OPV2 vaccination campaigns from May 2016 to 1 August 2024 were analyzed to estimate type-2 OPV-induced immunity in children under 5 years of age. Poliovirus surveillance data were used to estimate seeding dates and classify cVDPV2 emergences as mOPV2- or nOPV2-derived. The expected number of emergences if mOPV2 was used instead of nOPV2 was estimated, accounting for the timing and volume of nOPV2 doses, the known risk factors for emergence from mOPV2, and censoring due to the incomplete observation period for more recent nOPV2 doses. Results: As of 1 August 2024, over 98% of the approximately 1.19 billion nOPV2 doses administered globally were in Africa. We estimate that approximately 76 (95% confidence interval 69–85) index isolates of cVDPV2 emergences would be expected to be detected by 1 August 2024 if mOPV2 had been used instead of nOPV2 in Africa. The 18 observed nOPV2-derived emergences represent a 76% (74–79%) lower risk of emergence by nOPV2 than mOPV2 in Africa. The crude global analysis produced similar results. Key limitations include the incomplete understanding of the drivers of heterogeneity in emergence risk across geographies and variance in the per-dose risk of emergence may be incompletely captured using known risk factors. Conclusions: These results are consistent with the accumulating clinical and field evidence showing the enhanced genetic stability of nOPV2 relative to mOPV2, and this approach has been implemented in near-real time to contextualize new findings during the roll-out of this new vaccine. While nOPV2 has resulted in new emergences of cVDPV2, the number of cVDPV2 emergences is estimated to be approximately four-fold lower than if mOPV2 had been used instead. Full article

In the Global Poliovirus Laboratory Network (GPLN), participation and successful completion in annual proficiency test (PT) panels has been a part of the WHO accreditation process for decades. The PT panel is a molecular external quality assessment (mEQA) that evaluates laboratory preparedness, technical proficiency, the accuracy of data interpretation, and result reporting. Using the Intratypic Differentiation (ITD) real-time RT-PCR kits from CDC, laboratories run screening assays and report results in accordance with the ITD algorithm to identify and type polioviruses. The mEQA panels consisted of 10 blinded, non-infectious lyophilized RNA transcripts, including programmatically relevant viruses and targets contained in the real-time PCR assays. Sample identities included wildtype, vaccine-derived (VDPV), Sabin-like polioviruses, enterovirus, and negatives, as well as categories of invalid and indeterminate. The performance of individual laboratories was assessed based on the laboratory’s ability to correctly detect and characterize the serotype/genotype identities of each sample. The scoring scheme assessed the laboratory readiness following GPLN guidelines. Laboratories receiving mEQA scores of 90 or higher passed the assessment, scores of less than 90 failed and required remedial actions and re-evaluation. In 2021 and 2022, 123 and 129 GPLN laboratories were invited to request the annual PT panel, and 118 and 127 laboratories submitted results, respectively. The overall results were good, with 86% and 91.5% of laboratories passing the PT panel on their first attempt in 2021 and 2022, respectively. Most labs scored the highest score of 100, and less than one quarter scored between 90 and 95. Less than 10% of submitting laboratories failed the PT, resulting in in-depth troubleshooting to identify root causes and remediations. Most of these laboratories were issued a second PT panel for repeat testing, and almost all laboratories passed the repeat PT panel. The results of the 2021 and 2022 annual mEQA PTs showed that, despite the COVID-19 pandemic, the performance remained high in the GPLN, with most labs achieving the highest score. For these labs, the real-time PCR assay updates that were implemented during 2021–2022 were carried out with full adherence to procedures and algorithms. Even initially failing labs achieved passing scores after remediation. Full article

Background: The serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread, causing the emergence of vaccine-derived poliovirus (VDPV2) and immunodeficiency-related vaccine-derived polioviruses (iVDPVs). In the United States, testing carried out by the CDC of type II iVDPV (iVDPV2) with human immune serum from the vaccine has shown that the presence of the virus poses a threat to eradication efforts. Methods: We analyzed the major neutralization sites of VP1, VP2, and VP3 of the iVDPV using bioinformatics techniques and homology modeling (SWISS-MODEL). The three amino acid residues 679, 680, and 141 of the P1 region changed, which had an impact on the spatial conformation of the viral-neutralizing site. We tested polio-vaccinated human sera and rabbit anti-Sabin II polyantibodies against a panel of iVDPV pseudoviruses. Results: The results demonstrated that the serum’s capacity to neutralize mutant pseudoviruses diminished when amino acid substitutions were introduced into the P1 encapsidated protein, particularly when 141 and 679 were mutated together. This study emphasizes the significance of continually monitoring individuals who are known to be immunocompromised and maintaining high vaccination rates in OPV-using communities. Full article

The Global Polio Eradication Initiative was adopted by Ghana in 1996, and through robust AFP surveillance was able to interrupt the circulation of wild poliovirus in 2008. However, the country suffered vaccine-derived poliovirus type 2 outbreaks in 2019 and 2022. We conducted a retrospective analysis of all AFP surveillance data received by the polio program in Ghana from 2018 to 2022. An analysis of the WHO performance indicators for evaluating a surveillance system was conducted using Epi Info 3.5.4 and Microsoft Excel. Of the 4832 cases investigated, 56.3% were males, 71.1% comprised children aged 5 years and below, and more than half (65.2%) had received a maximum of three doses of OPV. Over 77% (3028) had a fever at the onset of paralysis, and 67.8% had paralysis progression within 3 days. The non-polio AFP rate of ≥2 and the stool adequacy rate exceeded the target of ≥80% in nearly every study year. The proportion of non-polio enteroviruses isolated surpassed the target of ≥10% in all years except 2018. The AFP surveillance system in Ghana is sensitive and representative. Though the surveillance became more intensive and proactive during the outbreak, the system needs to focus on improving the completeness of the data as well as the timeliness of the arrival of stool specimens within 3 days of collection. Full article

As the world is approaching the eradication of wild poliovirus serotype 1, the last of the three wild types, the question of how to maintain a polio-free world becomes imminent. To mitigate the risk of sporadic vaccine-associated paralytic polio (VAPP) caused by oral polio vaccines (OPVs) that are routinely used in global immunization programs, the Polio Antivirals Initiative (PAI) was established in 2006. The primary goal of the PAI is to facilitate the discovery and development of antiviral drugs to stop the excretion of immunodeficiency-associated vaccine-derived poliovirus (iVDPV) in B cell-deficient individuals. This review summarizes the major progress that has been made in the development of safe and effective poliovirus antivirals and highlights the candidates that have shown promising results in vitro, in vivo, and in clinical trials. Full article