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Background: Novel oral poliovirus vaccine type 2 (nOPV2) has been engineered to improve the genetic stability of Sabin oral poliovirus vaccine (OPV) and reduce the emergence of circulating vaccine-derived polioviruses. This trial aimed to provide key safety and immunogenicity data required for nOPV2 licensure and WHO prequalification., Methods: This phase 3 trial recruited infants aged 18 to <52 weeks and young children aged 1 to <5 years in The Gambia. Infants randomly assigned to receive one or two doses of one of three lots of nOPV2 or one lot of bivalent OPV (bOPV). Young children were randomised to receive two doses of nOPV2 lot 1 or bOPV. The primary immunogenicity objective was to assess lot-to-lot equivalence of the three nOPV2 lots based on one-dose type 2 poliovirus neutralising antibody seroconversion rates in infants. Equivalence was declared if the 95% CI for the three pairwise rate differences was within the -10% to 10% equivalence margin. Tolerability and safety were assessed based on the rates of solicited adverse events to 7 days, unsolicited adverse events to 28 days, and serious adverse events to 3 months post-dose. Stool poliovirus excretion was examined. The trial was registered as PACTR202010705577776 and is completed., Findings: Between February and October, 2021, 2345 infants and 600 young children were vaccinated. 2272 (96·9%) were eligible for inclusion in the post-dose one per-protocol population. Seroconversion rates ranged from 48·9% to 49·2% across the three lots. The minimum lower bound of the 95% CIs for the pairwise differences in seroconversion rates between lots was -5·8%. The maximum upper bound was 5·4%. Equivalence was therefore shown. Of those seronegative at baseline, 143 (85·6%) of 167 (95% CI 79·4-90·6) infants and 54 (83·1%) of 65 (71·7-91·2) young children seroconverted over the two-dose nOPV2 schedule. The post-two-dose seroprotection rates, including participants who were both seronegative and seropositive at baseline, were 604 (92·9%) of 650 (95% CI 90·7-94·8) in infants and 276 (95·5%) of 289 (92·4-97·6) in young children. No safety concerns were identified. 7 days post-dose one, 78 (41·7%) of 187 (95% CI 34·6-49·1) infants were excreting the type 2 poliovirus., Interpretation: nOPV2 was immunogenic and safe in infants and young children in The Gambia. The data support the licensure and WHO prequalification of nOPV2., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests ET works for PT Biofarma who manufacture the novel oral poliovirus vaccine type 2 and the bivalent oral poliovirus vaccine used in this trial. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2) has been developed to be more genetically stable with similar tolerability and immunogenicity to that of Sabin type 2 vaccines to mitigate the risk of cVDPV2. We aimed to assess these aspects of nOPV2 in poliovirus vaccine-naive newborn infants., Methods: In this randomised, double-blind, controlled, phase 2 trial we enrolled newborn infants at the Matlab Health Research Centre, Chandpur, Bangladesh. We included infants who were healthy and were a single birth after at least 37 weeks' gestation. Infants were randomly assigned (2:1) to receive either two doses of nOPV2 or placebo, administered at age 0-3 days and at 4 weeks. Exclusion criteria included receipt of rotavirus or any other poliovirus vaccine, any infection or illness at the time of enrolment (vomiting, diarrhoea, or intolerance to liquids), diagnosis or suspicion of any immunodeficiency disorder in the infant or a close family member, or any contraindication for venipuncture. The primary safety outcome was safety and tolerability after one and two doses of nOPV2, given 4 weeks apart in poliovirus vaccine-naive newborn infants and the primary immunogenicity outcome was the seroconversion rate for neutralising antibodies against type 2 poliovirus, measured 28 days after the first and second vaccinations with nOPV2. Study staff recorded solicited and unsolicited adverse events after each dose during daily home visits for 7 days. Poliovirus neutralising antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. This study is registered on ClinicalTrials.gov, NCT04693286., Findings: Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to receive nOPV2 (n=220 [67%]) or placebo (n=110 [33%]). nOPV2 was well tolerated; 154 (70%) of 220 newborn infants in the nOPV2 group and 78 (71%) of 110 in the placebo group had solicited adverse events, which were all mild or moderate in severity. Severe unsolicited adverse events in 11 (5%) vaccine recipients and five (5%) placebo recipients were considered unrelated to vaccination. 306 (93%) of 330 infants had seroprotective maternal antibodies against type 2 poliovirus at birth, decreasing to 58 (56%) of 104 in the placebo group at 8 weeks. In the nOPV2 group 196 (90%) of 217 infants seroconverted by week 8 after two doses, when 214 (99%) had seroprotective antibodies., Interpretation: nOPV2 was well tolerated and immunogenic in newborn infants, with two doses, at birth and 4 weeks, resulting in almost 99% of infants having protective neutralising antibodies., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests ET is a full-time employee of the vaccine manufacturer, PT Bio Farma (Bandung, Indonesia). All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The international spread of poliovirus exposes all countries to the risk of outbreaks and is designated a Public Health Emergency of International Concern by WHO. This risk can be exacerbated in countries using inactivated polio vaccine, which offers excellent protection against paralysis but is less effective than oral vaccine against poliovirus shedding, potentially allowing circulation without detection of paralytic cases for long periods of time. Our study investigated the molecular properties of type 2 poliovirus isolates found in sewage with an aim to detect virus transmission in the community., Methods: We performed environmental surveillance in London, UK, testing sewage samples using WHO recommended methods that include concentration, virus isolation in cell culture, and molecular characterisation. We additionally implemented direct molecular detection and determined whole-genome sequences of every isolate using novel nanopore protocols., Findings: 118 genetically linked poliovirus isolates related to the serotype 2 Sabin vaccine strain were detected in 21 of 52 sequential sewage samples collected in London between Feb 8 and July 4, 2022. Expansion of environmental surveillance sites in London helped localise transmission to several boroughs in north and east London. All isolates have lost two key attenuating mutations, are recombinants with a species C enterovirus, and an increasing proportion (20 of 118) meet the criterion for a vaccine-derived poliovirus, having six to ten nucleotide changes in the gene coding for VP1 capsid protein., Interpretation: Environmental surveillance allowed early detection of poliovirus importation and circulation in London, permitting a rapid public health response, including enhanced surveillance and an inactivated polio vaccine campaign among children aged 1-9 years. Whole-genome sequences generated through nanopore sequencing established linkage of isolates and confirmed transmission of a unique recombinant poliovirus lineage that has now been detected in Israel and the USA., Funding: Medicines and Healthcare products Regulatory Agency, UK Health Security Agency, Bill & Melinda Gates Foundation, and National Institute for Health Research Medical Research Council., Competing Interests: Declaration of interests We declare no competing interests., (© 2022 Crown Copyright claimed by UK, Canadian or Australian Government employee. This is an Open Access article under the OGL 3.0 license.)

Next generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using attenuated Sabin strains that maintain patient safety benefits and immunogenicity of conventional inactivated vaccines while increasing manufacturing safety and lowering production costs, and on developing novel oral vaccines using modified Sabin strains that provide critical mucosal immunity but are further attenuated to minimize risk of reversion to neurovirulence. In addition, there is a push to improve the analytical tools for poliovirus vaccine characterization. Conventional and Sabin inactivated poliovirus vaccines typically rely on standard plate-based ELISA as in vitro D-antigen potency assays in combination with WHO international standards as calibrants. While widely utilized, the current D-antigen ELISA assays have a long time to result (up to 72 h), can suffer from lab-to-lab inconsistency due to non-standardized protocols and reagents, and are inherently singleplex. For D-antigen quantitation, we have developed the VaxArray Polio Assay Kit, a multiplexed, microarray-based immunoassay that uses poliovirus-specific human monoclonal antibodies currently under consideration as standardized reagents for characterizing inactivated Sabin and Salk vaccines. The VaxArray assay can simultaneously quantify all 3 poliovirus serotypes with a time to result of less than 3 h. Here we demonstrate that the assay has limits of quantification suitable for both bioprocess samples and final vaccines, excellent reproducibility and precision, and improved accuracy over an analogous plate-based ELISA. The assay is suitable for adjuvanted combination vaccines, as common vaccine additives and crude matrices do not interfere with quantification, and is intended as a high throughput, standardized quantitation tool to aid inactivated poliovirus vaccine manufacturers in streamlining vaccine development and manufacturing, aiding the global polio eradication effort., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

The aim of this study was to demonstrate the strength of combining immunochemical and biophysical analysis tools for assessing the quality of Sabin inactivated poliovirus vaccine (Sabin-IPV) bulk products. We assessed Sabin-IPV serotypes 1, 2 and 3 from six different manufacturers and evaluated their comparability through biosensor analysis and biophysical characterization methods, including tryptophan fluorescence and asymmetrical flow field-flow fractionation - multi-angle light scattering analysis. These methods enabled us to assess antigenic as well as conformational and structural integrity profiles, respectively. Based on Sabin-IPV samples that were subjected to accelerated storage conditions, we revealed that existing immunochemical methods exhibit remarkably similar trends to the results obtained by the biophysical characterization methods. While the results underpin that the comparability of Sabin-IPV bulk products of different manufacturers is weak, information about their quality can rapidly be obtained by using both immunochemical and biophysical methods. Furthermore, the study highlights that quality assessment of Sabin-IPV can be obtained through biophysical techniques can complement the assessments performed with monoclonal antibodies and suggests that similar techniques could be employed to characterize other enteroviruses., Competing Interests: Conflict of Interest Statement The authors declare there are no other conflicts of interest associated with this article., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this analysis was to explore the determinants of incomplete immunization in children aged 12-23 months., Study Design: A secondary analysis was conducted on cross-sectional survey data from Pakistan Demographic and Health survey 2017-2018., Methods: The present study was confined to children aged 12-23 months at the time of survey giving a sample size of 2048. Complete immunization was described as having received a dose of BCG (Bacille Calmette Guerin), four doses of oral polio vaccine (OPV0, OPV1, OPV2, and OPV3), three doses of pentavalent and pneumococcal vaccine, and one dose of measles vaccine. Multivariable logistic regression was used to explore the association between outcome and predictor variables., Results: The findings showed that the likelihood of being incompletely immunized was higher for the children of Baluchistan (adjusted odds ratio [aOR] = 6.38; 95% confidence interval [CI] = 4.18-9.71), Federally Administered Tribal Areas (aOR = 6.2; 95% CI = 3.97-9.71), Sindh (aOR = 3.24; 95% CI = 2.33-4.49), Khyber Pakhtunkhwa (aOR = 2.13; 95% CI = 1.54-2.97), Islamabad (aOR = 3.656; 95% CI = 2.34-5.69), and Gilgit Baltistan (aOR = 2.320; 95% CI = 1.50-3.57) relative to those of Punjabi children. Lower odds of partial vaccination were seen among the children of educated mothers (primary or higher) and those who were born at a health facility., Conclusion: Improving maternal literacy rate, providing easy access to health facilities, and minimizing regional disparities can improve the immunization status of children in Pakistan., (Copyright © 2022 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Neonatal immunisation includes vaccination in the first 4 weeks of life (Neonatal period) as well as in high-risk preterm infants in the first few months (until 44 weeks corrected gestational age). Neonates have an immature immune system, which renders them highly susceptible to life-threatening infections. This highlights the importance of vaccination in this vulnerable population; however, at the same time also making it challenging because of their inability to generate a protective immune response. Other challenges include interference from maternal antibodies and excessive skewing towards T Helper Cell Type 2 (Th2) immunity. Despite these challenges, several vaccines have been developed and proven safe and effective at birth. Presently, there are 3 vaccines - Hepatitis B vaccine, Bacillus Calmette-Guerine (BCG) and Oral Polio vaccine (OPV) widely used in neonates, which provides evidence that certain antigen-adjuvant combinations can elicit protective neonatal responses. This review focusses on current vaccinations in neonates, including preterm infants and highlights some novel approaches to enhance neonatal vaccination., Competing Interests: Declaration of competing interest The author has no conflicts of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Poliomyelitis is a worldwide disease that has nearly been eradicated thanks to the Global Polio Eradication Initiative. Nevertheless, the disease is currently still endemic in three countries. In this paper, we incorporate the vaccination in a two age-class model of polio dynamics. Our main objective is to see whether mandatory vaccination policy is needed or if polio could be almost eradicated by a voluntary vaccination. We perform game theoretical analysis and compare the herd immunity vaccination levels with the Nash equilibrium vaccination levels. We show that the gap between two vaccination levels is too large. We conclude that the mandatory vaccination policy is therefore needed to achieve a complete eradication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim of Study: Recombination is one of the major mechanisms of evolution in poliovirus. In this work, recombination was assessed in children during vaccination with OPV and among circulating vaccine strains isolated in Tunisia during the last 15 years in order to identify a possible role of recombination in the response to the vaccine or the acquisition of an increased transmissibility., Material and Methods: This study included 250 poliovirus isolates: 137 vaccine isolates, excreted by children during primary vaccination with OPV and 113 isolates obtained from acute flaccid paralytic (AFP) cases and healthy contacts. Recombination was first assessed using a double PCR-RFLP, and sequencing., Results: Nineteen per cent of recombinant strains were identified: 20% of strains excreted by vaccinees among 18% of circulating strains. The proportion of recombinant in isolates of serotype1 was very low in the two groups while the proportions of recombinants in serotypes 2 and 3 were different. In vaccinees, the frequency of recombinants in serotype3 decreased during the course of vaccination: 54% after the first dose, 32% after the second and 14% after the third dose., Conclusion: These results suggest that recombination enhances the ability of serotype3 vaccine strains to induce an immune response. Apart from recent vaccination, it may contribute to a more effective transmissibility of vaccine strains among human population., (Copyright © 2009 Elsevier Masson SAS. All rights reserved.)

In this study the antiviral activity of a panel of 18 out of 240 pyridazinamine analogues was evaluated against the Sabin strains of the three poliovirus types. We found one compound, R75761 which had a comparable 50% effective concentration (EC50) value against all three poliovirus Sabin strains. Virus multiplication was reduced by 10(4.0)-fold, 10(6.2)-fold and 10(6.6)-fold for poliovirus type 1, type 2 and type 3, respectively. R75761 could be considered as a lead compound for development of anti-poliovirus drugs to be used during the late stage of poliovirus eradication and beyond.

Background: A nucleotide change from U to C at position 472 in the 5' non-coding region of the type 3 poliovirus is associated with increased neurovirulence. Moreover, the proportion of type 3 polioviruses containing this mutation (472-C revertants) correlates with the neurovirulence of a particular sample. We used mutant analysis by PCR and restriction-enzyme cleavage (MAPREC) to estimate the neurovirulence of environmental samples obtained from Toyama prefecture, Japan., Methods: Sewage and river water were collected between October, 1993, and September, 1995, and concentrated samples were inoculated into three different cell types. Isolated type 3 viruses were analysed to determine whether they were derived from the live oral poliovirus vaccine strain; they were then tested for neurovirulence by MAPREC., Results: 29 type 3 strains were isolated--all of which were vaccine-derived. 16 (55%) comprised between 2% and 91% 472-C revertants by MAPREC and were expected to have high neurovirulence. The remaining strains included less than 0.25% revertants, and were regarded as attenuated viruses. Both types were isolated about 3 months after routine oral poliovirus vaccine administrations in May and October. Three strains isolated from river water were of the virulent type., Interpretation: Our results emphasise that there is an environmental risk of vaccine-associated paralytic poliomyelitis as long as live oral poliovirus vaccine is not replaced by inactivated polio vaccine.

We used a randomized trial to compare two polio vaccine pamphlets written on a sixth grade level--the vaccine information statement prepared by the Centers for Disease Control (CDC) and an easy-to-read pamphlet we developed (LSU)--for reading ability, comprehension and preference among 610 parents with a broad range of demographic characteristics. Parents at all reading levels and incomes preferred LSU (76% vs. 21%, P < 0.001). Although readers of LSU achieved significantly higher comprehension (65% vs. 60%, P < 0.05) this difference may not be clinically significant. The information items presented with instructional graphics were the only items on which differences in comprehension levels achieved both clinical and statistical significance. Comprehension was lowest for the CDC mandated information on risks and the National Injury Compensation. Our findings demonstrate that simplifying written immunization material and making it more suitable will increase appeal, but such modification may not raise comprehension to an acceptable level without use of instructional graphics. Health education materials intended for general parent populations, which are written on a sixth grade reading level, may not adequately educate parents or prepare them for a discussion with their physicians.

This study was carried out in the states of Lagos, Oyo, Osun, Nigeria and was designed to assess the efficiency of the cold chain and the potency of the vaccines from the National Cold Store through to the vaccination centres. Storage equipment was inspected and oral polio, measles and yellow fever vaccines were tested for potency. All 27 centres studied had adequately trained staff and storage was shown to be adequate at the National and State Cold Store Level. However, vaccines were adversely affected at the local Government Area Cold Store and Vaccination Centre Levels. Losses of potency of vaccines were shown: loss of titre of oral polio and yellow fever vaccine (0.03-0.9 log) was less than that of the measles vaccines (0.1-2.7 log). This was ascribed to thawing and refreezing due to equipment failure, to intermittent power supply in the absence of standby generators and mishandling of vaccines in the vaccine centres. This study revealed inadequacies at the Local Government Area and Vaccination Centre level. The cold chain should be examined in the remaining states of Nigeria and the inadequacies corrected.