Search Results (47)

Background/Objectives: Most Japanese adults received two doses of the oral polio vaccine (OPV) during childhood as part of the national immunization program. However, these two doses are considered suboptimal by global standards. The long-term persistence of anti-poliovirus antibodies after booster doses with the conventional inactivated poliovirus vaccine (cIPV) in Japanese adults remains unclear. This study was performed to evaluate long-term immunogenicity over a 10-year period following two cIPV booster vaccinations. Methods: Ten out of sixty-one adult participants in a short-term study were enrolled to assess the long-term immunogenicity of the booster vaccination. They underwent blood sampling at 3, 5, and 10 years after cIPV vaccination. Results: The results indicate that, even 10 years after the booster vaccination, antibodies against poliovirus types 1 and 2 remained at high levels, exceeding the detection limits of neutralization tests. However, some participants showed decreased antibody levels against poliovirus type 3. Conclusions: This study showed that cIPV boosters provided long-lasting protective immunity against poliovirus types 1 and 2 in adults who were vaccinated with OPV. These findings are valuable in assessing the need for IPV booster vaccinations in adults. 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

Background/Objectives: As we commemorate 50 years of the Expanded Programme on Immunization (EPI), the global mission to eradicate polio stands at a critical juncture. While remarkable progress has been made over the past decades, ensuring a steady supply of polio vaccines remains a significant challenge that could undermine these achievements. This manuscript aims to address the complexities of polio vaccine security within the context of the Immunization Agenda 2030 (IA2030) and the Global Polio Eradication Strategy 2022–2029, proposing actionable strategies to strengthen the vaccine supply. Methods: This manuscript analyzes obstacles to vaccine security, including supply disruptions and market uncertainties. It presents the Polio Vaccine Security Framework as a key strategy for addressing these challenges. Data were gathered from Global Polio Eradication Initiative (GPEI) reports, consultations with key stakeholders, and analyses of past vaccine shortages. Results: The findings indicate that the primary risks to vaccine security include the lack of a coherent long-term policy framework on polio vaccination, the absence of a clear polio vaccine development roadmap, and insufficient long-term, predictable forecasting. Additionally, stronger coordination is needed between stakeholders involved in vaccine supply, polio containment, and research, as well as addressing challenges related to financing and access to resources. Conclusions: A robust, adaptable, and sustainable approach to vaccine security, proposed in the Polio Vaccine Security Framework, is critical to achieving and sustaining polio eradication. Collaboration among policymakers, manufacturers, and stakeholders to implement it is essential to ensure the uninterrupted supply of polio vaccines, protecting the progress made over the past half century, and preventing a resurgence of poliovirus in the future. Full article

Background: Uganda’s Integrated Child Health Day (ICHD) initiative aims to improve children’s access to vaccinations. Although widely used as a catch-up vaccination strategy, the effectiveness of the ICHD program in increasing immunization coverage, especially among vulnerable populations, has not been recently evaluated. This study assessed the reach and uptake of ICHD for immunizations in Uganda. Methods: A mixed-methods evaluation was conducted in three districts (Rakai, Kayunga, and Bukedea) where ICHDs occurred. The data collection included a cross-sectional household survey using validated WHO-adapted questionnaires of 1432 caregivers of children under five years old, key informant interviews with 42 health managers and workers, and nine focus group discussions with caregivers between October and December 2022. The vaccines assessed were Bacillus Calmette–Guerin, oral polio, Pentavalent, pneumococcal conjugate, rotavirus (RV), and measles-rubella (MR). Results: The immunization coverage based on child health cards was over 90% for all vaccines except for the second dose of RV (88.3%) and MR (16.2%). Among the children, 2.3% had received no Pentavalent vaccine, and 69.4% were fully vaccinated for their age. Of the 631 children who attended ICHDs, 79.4% received at least one vaccine during the event. Village Health Teams (49%), health workers (18.3%), and megaphone outreach (17.9%) were the primary information sources. Key informants cited challenges with coordination, vaccine delivery, and mobilization. Conclusions: Despite operational challenges, ICHDs appear to have contributed to routine childhood vaccinations. Further research is needed to assess the sustainability and cost-effectiveness of the program. 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

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

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

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively). Both PV2 wtVLP and sVLP are efficiently produced in Pichia pastoris yeast. The PV2 sVLP displays higher levels of D-antigen and significantly enhanced thermostability than the wtVLP. Unlike the wtVLP, the sVLP elicits neutralizing antibodies in mice at levels comparable to those induced by inactivated polio vaccine. The addition of an aluminum hydroxide adjuvant to sVLP results in faster induction and a higher magnitude of neutralizing antibodies. Furthermore, our cryo-EM structural study of both sVLP and wtVLP reveals a native conformation for the sVLP and a non-native expanded conformation for the wtVLP. Our work not only validates the yeast-produced PV2 sVLP as a promising vaccine candidate with high production potential but also sheds light on the structural mechanisms that underpin the assembly and immunogenicity of the PV2 sVLP. These findings may expedite the development of sVLP-based PV vaccines. Full article

In 2022, global poliovirus modeling suggested that coordinated cessation of bivalent oral poliovirus vaccine (bOPV, containing Sabin-strain types 1 and 3) in 2027 would likely increase the risks of outbreaks and expected paralytic cases caused by circulating vaccine-derived polioviruses (cVDPVs), particularly type 1. The analysis did not include the implementation of planned, preventive supplemental immunization activities (pSIAs) with bOPV to achieve and maintain higher population immunity for types 1 and 3 prior to bOPV cessation. We reviewed prior published OPV cessation modeling studies to support bOPV cessation planning. We applied an integrated global poliovirus transmission and OPV evolution model after updating assumptions to reflect the epidemiology, immunization, and polio eradication plans through the end of 2023. We explored the effects of bOPV cessation in 2027 with and without additional bOPV pSIAs prior to 2027. Increasing population immunity for types 1 and 3 with bOPV pSIAs (i.e., intensification) could substantially reduce the expected global risks of experiencing cVDPV outbreaks and the number of expected polio cases both before and after bOPV cessation. We identified the need for substantial increases in overall bOPV coverage prior to bOPV cessation to achieve a high probability of successful bOPV cessation. Full article

In the context of polio eradication, novel oral polio vaccines for type 2 (nOPV2) were developed, and types 1 and 3 polioviruses are being developed. We aimed to generate trivalent oral poliovirus vaccine (tOPV) safety and immunogenicity data as a reference for comparing with novel OPV formulations. This was a single-center, open-label, phase 4 study in March 2016 in the Dominican Republic with healthy children previously vaccinated with ≥3 doses of tOPV receiving one dose of tOPV and vaccine-naïve infants receiving 3 doses of tOPV. Safety and immunogenicity were assessed. No serious adverse reactions or important medical reactions were reported. Seroconversion (SC) rates at Day 28 in children were 32.7%, 36.7%, and 46.9% for types 1, 2, and 3, respectively, and seroprotection (SP) rates 28 days after one dose increased from 89.8% at baseline to 93.9%, 98.0% to 100%, and 83.7% to 98.0% for types 1, 2, and 3, respectively. In infants, SC rates were 88.5%, 98.1%, and 96.2% for types 1, 2, and 3, respectively. SP rates at Day 84 were 93.3%, 100%, and 96.2% for types 1, 2, and 3, respectively. This information can be used as a reference to compare with novel monovalent or trivalent OPVs under development. Full article

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021–April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being. Full article

Continued investment in the development and application of mathematical models of poliovirus transmission, economics, and risks leads to their use in support of polio endgame strategy development and risk management policies. This study complements an earlier review covering the period 2000–2019 and discusses the evolution of studies published since 2020 by modeling groups supported by the Global Polio Eradication Initiative (GPEI) partners and others. We systematically review modeling papers published in English in peer-reviewed journals from 2020–2024.25 that focus on poliovirus transmission and health economic analyses. In spite of the long-anticipated end of poliovirus transmission and the GPEI sunset, which would lead to the end of its support for modeling, we find that the number of modeling groups supported by GPEI partners doubled and the rate of their publications increased. Modeling continued to play a role in supporting GPEI and national/regional policies, but changes in polio eradication governance, decentralized management and decision-making, and increased heterogeneity in modeling approaches and findings decreased the overall impact of modeling results. Meanwhile, the failure of the 2016 globally coordinated cessation of type 2 oral poliovirus vaccine use for preventive immunization and the introduction of new poliovirus vaccines and formulation, increased the complexity and uncertainty of poliovirus transmission and economic models and policy recommendations during this time. Full article

Background: In 2016, the Global Polio Eradication Initiative (GPEI) recommended the cessation of using type 2 oral poliovirus vaccine (OPV) and OPV, with countries having to switch from the trivalent to bivalent OPV (bOPV) with the addition of inactivated poliovirus vaccine (IPV) in their routine immunization schedule. The current GPEI strategy 2022–2026 includes a bOPV cessation plan and a switch to IPV alone or a combination of vaccine schedules in the future. The focus of our study was to evaluate the immunogenicity of monovalent OPV type 1 (mOPV1) with IPV and IPV-only schedules. Methods: This was a three-arm, multi-center randomized–controlled trial conducted in 2016–2017 in India. Participants, at birth, were randomly assigned to the bOPV-IPV (Arm A) or mOPV1-IPV (Arm B) or IPV (Arm C) schedules. Serum specimens collected at birth and at 14, 18, and 22 weeks old were analyzed with a standard microneutralization assay for all the three poliovirus serotypes. Results: The results of 598 participants were analyzed. The type 1 cumulative seroconversion rates four weeks after the completion of the schedule at 18 weeks were 99.5% (97.0–99.9), 100.0% (97.9–100.0), and 96.0% (92.0–98.1) in Arms A (4bOPV + IPV), B (4mOPV1 + IPV), and C (3IPV), respectively. Type 2 and type 3 seroconversions at 18 weeks were 80.0% (73.7–85.1), 76.9% (70.3–82.4); 93.2% (88.5–96.1), 100.0% (98.0–100.0); and 81.9% (75.6–86.8), 99.4% (96.9–99.9), respectively, in the three arms. Conclusions: This study shows the high efficacy of different polio vaccines for serotype 1 in all three schedules. The type 1 seroconversion rate of mOPV1 is non-inferior to bOPV. All the vaccines provide high type-specific immunogenicity. The program can adopt the use of different vaccines or schedules depending on the epidemiology from time to time. Full article

As the Global Polio Eradication Initiative (GPEI) strategizes towards the final steps of eradication, routine immunization schedules evolve, and high-quality vaccination campaigns and surveillance systems remain essential. New tools are consistently being developed, such as the novel oral poliovirus vaccine to combat outbreaks more sustainably, as well as non-infectiously manufactured vaccines such as virus-like particle vaccines to eliminate the risk of resurgence of polio on the eve of a polio-free world. As the GPEI inches towards eradication, re-strategizing in the face of evolving challenges and preparing for unknown risks in the post-certification era are critical. Full article

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe. Full article