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In the context of polio eradication efforts, accurate assessment of vaccination programme effectiveness is essential to public health planning and decision making. Such assessments are often based on zero-dose children, estimated using the number of children who did not receive the first dose of the Diphtheria-Tetanus-Pertussis containing vaccine as a proxy. Our study introduces a novel approach to directly estimate the number of children susceptible to poliovirus type 2 (PV2) and uses this approach to provide district-level estimates for South Africa of susceptible children born between 2017 and 2022. We used district-level data on annual doses of inactivated poliovirus vaccine (IPV) administered, live births, and population sizes, from 2017 through 2022. We imputed missing vaccination data, implemented flexible assumptions regarding dose distribution in the eligible population, and used estimated efficacy values for one, two, three, and four doses of IPV, to compute the number of susceptible and immune children by birth year. We validated our approach by comparing an intermediary output with zero-dose children (ZDC) estimated using data reported by WHO/UNICEF Estimates of National Immunization Coverage (WUENIC). Our results indicate high heterogeneity in susceptibility to PV2 across South Africa's 52 districts as of the end of 2022. In children under 5 years, PV2 susceptibility ranged from approximately 30 % in districts including Xhariep (31.9 %), Ekurhuleni (30.1 %), and Central Karoo (29.8 %), to less than 4 % in Sarah Baartman (1.9 %), Buffalo City (2.1 %), and eThekwini (3.2 %). Our susceptibility estimates were consistently higher than ZDC over the timeframe. We estimated that ZDC decreased nationally from 155,168 (152,737-158,523) in 2017 to 108,593 in 2021, and increased to 127,102 in 2022, a trend consistent with ZDC derived from data reported by WUENIC. While our approach provides a more comprehensive profile of PV2 susceptibility, our susceptibility and ZDC estimates generally agree in the ranking of districts according to risk., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

This study assesses poliovirus type 1 (PV1) immunity in children to inform the contribution of mucosal immunity in and prevention of poliovirus circulation. A community-based study was conducted in periurban Karachi, Pakistan. Randomly selected children (0-15 years of age) received oral poliovirus vaccine (OPV) challenge dose. Blood and stool samples were collected at several time points and evaluated for polio-neutralizing antibodies and serotype-specific poliovirus, respectively. Eighty-one of 589 (14%) children excreted PV1 7 days post-OPV challenge; 70 of 81 (86%) were seropositive at baseline. Twelve of 610 (2%) were asymptomatic wild poliovirus type 1 (WPV1) excretors. Most poliovirus excretors had humoral immunity, suggesting mucosal immunity in these children likely waned or never developed. Without mucosal immunity, they are susceptible to poliovirus infection, shedding, and transmission. Asymptomatic WPV1 excretion suggests undetected poliovirus circulation within the community., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May-August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = -3% [90% confidence interval: -6 - 0.4%]; type 3 difference: -3% [-6 to -0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Khalequ Zaman, Asma Binte Aziz, Mohammad Yunus, Warda Haque b reports financial support was provided by Centers for Disease Control and Prevention. Cynthia J Snider’s spouse previously owned stock in Sanofi Pasteur, (Published by Elsevier Ltd.)

Patients with Primary immunodeficiency (PIDs) may be infected by Polioviruses (PVs), especially when vaccinated with live Oral Polio Vaccine before diagnosis. They may establish long-term shedding of divergent strains and may act as reservoirs of PV transmission. This study delved into the effect of the genetic evolution of complete PV genomes, from MHC class II-deficient patients, on the excretion duration and clinical outcomes. Stool samples from three PID patients underwent analysis for PV detection through inoculation on cell culture and real-time PCR, followed by VP1 partial sequencing and full genome sequencing using the Illumina technology. Our findings revealed a low number of mutations for one patient who cleared the virus, while two exhibited a high intra-host diversity favoring the establishment of severe outcomes. Neurovirulence-reverse mutations were detected in two patients, possibly leading to paralysis development. Furthermore, a recombination event, between type 3 Vaccine-Derived Poliovirus and Sabin-like1 (VDPV3/SL1), occurred in one patient. Our findings have suggested an association between intra-host diversity, recombination, prolonged excretion of the virus, and emergence of highly pathogenic strains. Further studies on intra-host diversity are crucial for a better understanding of the virus evolution as well as for the success of the Global Polio Eradication Initiative., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Objectives: This study aims to evaluate the safety of a new inactivated poliomyelitis vaccine (Sabin strains) (sIPV) for large-scale use in primary and booster immunizations, whether simultaneously administered with other vaccines or not and to explore the persistence of all vaccines at approximately six months after vaccination., Method: A total of 3200 infants were recruited into this study, including 2000 infants aged 2-3 months randomly assigned (1:1) into the "sIPV basic" or the "sIPV+DTaP" group for primary immunization of sIPV. Another 1200 children aged 18 months old and above were randomly assigned (2:2:1:1) into the "sIPV booster," "sIPV+HepA-I," "sIPV+MMR", or "sIPV+HepA-L" group for booster immunization of sIPV. Adverse events within 30 days of each vaccination dose in all participants were self-reported by guardians using a WeChat mini-program. Approximately 200 blood samples were collected at 5-7 months after the final vaccination to test for antibodies against poliovirus and other viruses., Results: 3198 participants in total were included in the safety study, including 1999 infants aged 2-3 months old and 1199 children aged 18-26 months old. For primary immunization, the incidence of adverse reactions in the "sIPV basic" and the "sIPV+DTaP" group were 3.19 and 6.21% (P = 0.001), respectively. For booster immunization, the incidences of adverse reaction for the "sIPV booster" group were 2.25%, while the incidence for the "sIPV +others" group in total was 2.50% (P = 0.788). Most adverse reactions were mild. Fever was the most common symptom in all groups. No vaccine-related serious adverse events (SAEs) were observed in this study. The seropositivity rates of antibodies in the "sIPV basic" and the "sIPV+DTaP" group were 92.31 and 100% against type 1 poliovirus (P = 0.031); 96.15% and 98.57% against type 2 poliovirus (P = 0.575); 98.08% and 91.43% against type 3 poliovirus (P = 0.237), respectively. Regarding booster vaccination with sIPV, whether co-administered with other vaccines or not, the seropositivity rates of antibodies against the three types of polioviruses were all 100%. Seropositivity rates of antibodies against hepatitis A, measles, mumps, and rubella were all no <77%, except for pertussis, which was <30%., Conclusion: sIPV demonstrated good safety and immune persistence for primary and booster vaccinations, whether administered singly or simultaneously. Antibodies against hepatitis A, measles, mumps and rubella were not disrupted by the co-vaccination. However, the seropositivity rates and geometric mean concentrations (GMCs) of antibodies against pertussis indicate the necessity for a booster dose., 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 © 2024. Published by Elsevier Ltd.)

Background: Poliovirus is a highly infectious enterovirus (EV) that primarily affects children and can lead to lifelong paralysis or even death. Vaccine-derived polioviruses (VDPVs) are a great threat since they are derived from the attenuated virus in the Oral Poliovirus Vaccine (OPV) and can mutate to a more virulent form. The purpose of this study was to identify VDPV serotype 2 through the year 2020-2021 via surveillance of sewage samples collected from different localities and governorates in Egypt and stool specimens from Acute Flaccid Paralysis (AFP) cases. Both were collected through the national poliovirus surveillance system and according to the guidelines recommended by the WHO., Methods: A total of 1266 sewage samples and 3241 stool samples from January 2020 to December 2021 were investigated in the lab according to World Health Organization (WHO) protocol for the presence of Polioviruses by cell culture, molecular identification of positive isolates on L20B cell line was carried out using real-time polymerase chain reactions (RT-PCR). Any positive isolates for Poliovirus type 2 and isolates suspected of Vaccine Derived Poliovirus Type 1 and type 3 screened by (VDPV1) or Vaccine Poliovirus Type 3 (VDPV3) assay in RT-PCR were referred for VP1 genetic sequencing., Results: The outbreak was caused by circulating VDPV2 (cVDPV2) strains started in January 2021. By the end of February 2021, a total of 11 cVDPV2s were detected in sewage samples from six governorates confirming the outbreak situation. One additional cVDPV2 was detected later in the sewage sample from Qena (June 2021). The first and only re-emergence of VDPV2 in stool samples during the outbreak was in contact with Luxor in June 2021. By November 2021, a total of 80 VDPVs were detected. The Egyptian Ministry of Health and Population (MOHP), in collaboration with the WHO, responded quickly by launching two massive vaccination campaigns targeting children under the age of five. Additionally, surveillance systems were strengthened to detect new cases and prevent further spread of the virus., Conclusion: The continued threat of poliovirus and VDPVs requires ongoing efforts to prevent their emergence and spread. Strategies such as improving immunization coverage, using genetically stable vaccines, and establishing surveillance systems are critical to achieving global eradication of poliovirus and efficient monitoring of VDPVs outbreaks., (© 2024. The Author(s).)

Aims: To explore if intestinal immunity induced by infection with live viruses in the oral poliovirus vaccine (OPV) is essential, necessary or even helpful in interrupting transmission of wild poliovirus (WPV) for global polio eradication., Methods: We reviewed the biology of virus-host interactions in WPV infection and its alterations by OPV-induced immunity for direct evidence of the usefulness of intestinal immunity. We also explored indirect evidence by way of the effect of the inactivated poliovirus vaccine (IPV) on the biology and on transmission dynamics of WPV., Results: Immunity, systemic and intestinal, induced by infection with WPV or vaccine viruses, does not prevent re-infection with WPV or vaccine viruses respectively, when exposed. Such re-infected hosts shed virus in the throat and in faeces and are sources of further transmission. Immunity protects against polio paralysis-hence reinfection always remain asymptommatic and silent., Conclusion: Vaccine virus-induced intestinal immunity is not necessary for polio eradication. The continued and intensive vaccination efforts using OPV under the assumption of its superiority over IPV have resulted in the well-known undesirable effects, namely vaccine associated paralytic polio and the emergence of de-attenuated circulating vaccine-derived polioviruses, in addition to the delay in completing global WPV eradication.

Background: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV)., Methods: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose., Results: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group., Conclusions: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China., (© 2024. The Author(s).)

With continued wild poliovirus transmission in Afghanistan and Pakistan and circulating vaccine-derived poliovirus in certain countries, there exists an ongoing risk of importation of polioviruses into other countries, including those that have been polio-free for decades. Diversifying the poliovirus outbreak response toolkit is essential to account for different public health and epidemiological contexts. In this Personal View, we discuss data on intestinal and pharyngeal mucosal immunity induced by inactivated poliovirus vaccine (IPV), previous programmatic experience of poliovirus outbreak response with IPV, and outbreak response guidelines in countries that exclusively use IPV. With recent reports of poliovirus detection in polio-free countries such as the USA and the UK, it is important to assess the interplay of virus transmission dynamics, vaccine impact on preventing paralysis and virus spread, and regulatory complexities of using oral poliovirus vaccine (OPV) and IPV options for outbreak response. As the global eradication programme navigates through cessation of routine OPV use with replacement by IPV and stockpiling of novel OPVs, clarity on the impact of IPV use will be important for informed decision making by global, regional, and national policy makers., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate antibody responses in humans and animals that can recognize members of multiple enterovirus species. However, cross protective immunity across multiple enteroviruses is not observed epidemiologically in humans. Here we investigated whether immunization of mice or baboons with inactivated poliovirus or enterovirus virus-like-particles (VLPs) vaccines generates antibody responses that can recognize enterovirus D68 or A71. We found that mice only generated antibodies specific for the antigen they were immunized with, and repeated immunization failed to generate cross-reactive antibody responses as measured by both ELISA and neutralization assay. Immunization of baboons with IPV failed to generate neutralizing antibody responses against enterovirus D68 or A71. These results suggest that a multivalent approach to enterovirus vaccination is necessary to protect against enterovirus disease in vulnerable populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but non-zero risk of paralysis with oral poliovirus vaccines (OPVs), countries that achieve and maintain high national routine immunization coverage have increasingly shifted to exclusive use of inactivated poliovirus vaccine (IPV) for all preventive immunizations. However, immunization coverage within countries varies, with under-vaccinated subpopulations potentially able to sustain transmission of imported polioviruses and experience local outbreaks. Due to its cost, ease-of-use, and ability to induce mucosal immunity, using OPV as an outbreak control measure offers a more cost-effective option in countries in which OPV remains in use. However, recent polio outbreaks in IPV-only countries raise questions about whether and when IPV use for outbreak response may fail to stop poliovirus transmission and what consequences may follow from using OPV for outbreak response in these countries. We systematically reviewed the literature to identify modeling studies that explored the use of IPV for outbreak response in IPV-only countries. In addition, applying a model of the 2022 type 2 poliovirus outbreak in New York, we characterized the implications of using different OPV formulations for outbreak response instead of IPV. We also explored the hypothetical scenario of the same outbreak except for type 1 poliovirus instead of type 2. We find that using IPV for outbreak response will likely only stop outbreaks for polioviruses of relatively low transmission potential in countries with very high overall immunization coverage, seasonal transmission dynamics, and only if IPV immunization interventions reach some unvaccinated individuals. Using OPV for outbreak response in IPV-only countries poses substantial risks and challenges that require careful consideration, but may represent an option to consider for some outbreaks in some populations depending on the properties of the available vaccines and coverage attainable., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kid Risk authors (KMT, DAK, KB) reports financial support was provided by Centers for Disease Control and Prevention. Kid Risk authors (KMT, DAK, KB) reports a relationship with Centers for Disease Control and Prevention that includes: funding grants., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite multiple revisions of targets and timelines in polio eradication plans since 1988, including changes in supplemental immunization activities (SIAs) that increase immunity above routine immunization (RI) coverage, poliovirus transmission continues as of 2024., Methods: We reviewed polio eradication plans and Global Polio Eradication Initiative (GPEI) annual reports and budgets to characterize key phases of polio eradication, the evolution of poliovirus vaccines, and the role of SIAs. We used polio epidemiology to provide context for successes and failures and updated prior modeling to show the contribution of SIAs in achieving and maintaining low polio incidence compared to expected incidence for the counterfactual of RI only., Results: We identified multiple phases of polio eradication that included shifts in targets and timelines and the introduction of different poliovirus vaccines, which influenced polio epidemiology. Notable shifts occurred in GPEI investments in SIAs since 2001, particularly since 2016. Modeling results suggest that SIAs play(ed) a key role in increasing (and maintaining) high population immunity to levels required to eradicate poliovirus transmission globally., Conclusions: Shifts in polio eradication strategy and poliovirus vaccine usage in SIAs provide important context for understanding polio epidemiology, delayed achievement of polio eradication milestones, and complexity of the polio endgame.

Background: According to Polio Eradication and Endgame Strategic Plan 2019-2023 (PEESP), countries that achieved wild polio elimination is expected to replace oral polio vaccine (OPV) which has a risk of vaccine-derived poliovirus, Inactivated Polio Vaccine (IPV). It is important to determine the earliest time in the age of a child at which IPV could be introduced into the country's routine immunization schedule for effectiveness especially as it concerns neutralizing effect of trans-placental transmitted antibodies which usually does not affect OPV. In this study, the level of poliovirus neutralizing antibody titre among neonates at birth was evaluated., Methods: A cross-sectional study of mother-baby pair. The serum level of the neutralizing Poliovirus antibody IgG titre was done by the Enzyme Linked Immunosorbent Assay (ELISA) technique., Results: There was 100% transfer of maternal passive antibodies to their babies. The mean poliovirus antibody titre among neonates was 21.8 IU/L which was above the neutralizing titre level. Most (85.7%) babies antibody level correlate positively with that of their mothers., Conclusion: The transferred maternal antibodies to the babies are still very high at birth, and capable of dampening the immunity of IPV if introduced early. Programme managers should evaluate the impact and benefit of given booster dose of IPV to pregnant mothers to increase the titre level in their babies. This will be very necessary when the OPV is withdrawn from the immunization schedule., 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 © 2023 Elsevier Ltd. All rights reserved.)

Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence 1-3 resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication., (© 2023. The Author(s).)

The presence of maternal poliovirus antibodies may interfere with the immune response to inactivated polio vaccine (IPV), and its influence on the safety of vaccination is not yet understood. A total of 1146 eligible infants were randomly assigned (1:1) to the IPV and Sabin IPV (SIPV) groups to compare and analyze the efficacy of the two vaccines in preventing poliovirus infection. We pooled the SIPV and IPV groups and reclassified them into the maternal poliovirus antibody-positive group (MAPG; ≥1: 8) and the maternal poliovirus antibody-negative group (MANG; <1: 8). We evaluated the impact of maternal poliovirus antibodies by comparing the geometric mean titer (GMT), seroconversion rate, and geometric mean increase (GMI) of types I-III poliovirus neutralizing antibodies post-vaccination, and incidence rates of adverse reactions following vaccination between the MAPG and MANG. Respective seroconversion rates in the MAPG and MANG were 94% and 100%, 79.27% and 100%, and 93.26% and 100% (all serotypes, P  < .01) for types I-III poliovirus, respectively. The GMT of all types of poliovirus antibodies in the MAPG (1319.13, 219.91, 764.11, respectively) were significantly lower than those in the MANG (1584.92, 286.73, 899.59, respectively) ( P  < .05). The GMI in the MAPG was significantly lower than that in the MANG ( P  < .05). No statistically significant difference in the incidence of local and systemic adverse reactions was observed between the MAPG and MANG. Thus, the presence of maternal poliovirus antibodies does not affect the safety of IPV but can negatively impact the immune responses in infants after IPV vaccination.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Pakistan and Afghanistan remain the only reservoirs of wild poliovirus transmission. Prior modeling suggested that before the coronavirus disease 2019 (COVID-19) pandemic, plans to stop the transmission of serotype 1 wild poliovirus (WPV1) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2) did not appear on track to succeed., Methods: We updated an existing poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model for Pakistan and Afghanistan to characterize the impacts of immunization disruptions and restrictions on human interactions (ie, population mixing) due to the COVID-19 pandemic. We also consider different options for responding to outbreaks and for preventive supplementary immunization activities (SIAs)., Results: The modeling suggests that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on 1 January 2021 of all polio immunization activities to pre-COVID-19 levels, Pakistan and Afghanistan would remain off-track for stopping all transmission through 2023 without improvements in quality., Conclusions: Using trivalent OPV (tOPV) for SIAs instead of serotype 2 monovalent OPV offers substantial benefits for ending the transmission of both WPV1 and cVDPV2, because tOPV increases population immunity for both serotypes 1 and 2 while requiring fewer SIA rounds, when effectively delivered in transmission areas., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Both inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV) have contributed to the rapid disappearance of paralytic poliomyelitis from developed countries despite possessing different vaccine properties. Due to cost, ease of use, and other properties, the Expanded Programme on Immunization added OPV to the routine infant immunization schedule for low-income countries in 1974, but variable vaccine uptake and impaired immune responses due to poor sanitation limited the impact. Following launch of the Global Polio Eradication Initiative in 1988, poliomyelitis incidence has been reduced by >99% and types 2 and 3 wild polioviruses are now eradicated, but progress against type 1 polioviruses which are now confined to Afghanistan and Pakistan has slowed due to insecurity, poor access, and other problems. A strategic, globally coordinated replacement of trivalent OPV with bivalent 1, 3 OPV in 2016 reduced the incidence of vaccine-associated paralytic poliomyelitis (VAPP) but allowed the escape of type 2 vaccine-derived polioviruses (VDPV2) in areas with low immunization rates and use of monovalent OPV2 in response seeded new VDPV2 outbreaks and reestablishment of type 2 endemicity. A novel, more genetically stable type 2 OPV vaccine is undergoing clinical evaluation and may soon be deployed prevent or reduce VDPV2 emergences., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Environmental surveillance was recommended for risk mitigation in a novel oral polio vaccine-2 (nOPV2) clinical trial (M5-ABMG) to monitor excretion, potential circulation, and loss of attenuation of the two nOPV2 candidates. The nOPV2 candidates were developed to address the risk of poliovirus (PV) type 2 circulating vaccine-derived poliovirus (cVDPV) as part of the global eradication strategy. Between November 2018 and January 2020, an environmental surveillance study for the clinical trial was conducted in parallel to the M5-ABMG clinical trial at five locations in Panama. The collection sites were located upstream from local treatment plant inlets, to capture the excreta from trial participants and their community. Laboratory analyses of 49 environmental samples were conducted using the two-phase separation method. Novel OPV2 strains were not detected in sewage samples collected during the study period. However, six samples were positive for Sabin-like type 3 PV, two samples were positive for Sabin-like type 1 PV, and non-polio enteroviruses NPEVs were detected in 27 samples. One of the nOPV2 candidates has been granted Emergency Use Listing by the World Health Organization and initial use started in March 2021. This environmental surveillance study provided valuable risk mitigation information to support the Emergency Use Listing application.

Background: Fractional dose (one-fifth of full intramuscular dose) of inactivated poliovirus vaccine (fIPV) administered intradermally is used as IPV dose-sparing strategy. We compared the rate of decline of poliovirus antibodies (PVA) in recipients of 2 doses of fIPV or IPV., Methods: A community-based randomized controlled trial was conducted in Karachi, Pakistan. Children aged 14 weeks were randomized into fIPV or full IPV (study arms A, B) and received 1 vaccine dose at age 14 weeks and 1 at age 9 months. PVAs were measured at age 14, 18 weeks and 10, 21 months., Results: Seroprevalence of poliovirus type 2 antibodies in 170/250 (68%) children after 2 IPV or fIPV doses at age 10 months in A and B reached 100% vs 99% (P = .339), and at 21 months, 86% vs 67% (P = .004). Between age 10 and 21 months antibody log2 titers dropped from ≥ 10.5 to 6.8 in A and from 9.2 to 3.7 in B., Conclusions: There was a significant decline in antibody titers 12 months following the second IPV dose. The slope of decline was similar for full IPV and fIPV recipients. The results provide further evidence that fIPV is a viable option for IPV dose-sparing., Clinical Trials Registration: NCT03286803., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation., Methods: An open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections., Results: PVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months., Conclusion: Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients., Trial Registration Number: NCT03712358., Competing Interests: Competing interests: SKN owns intellectual property related to this research, which has been licensed to Istari Oncology, Inc. DDB and MG have financial interest in Istari Oncology, Inc. Duke University (Licensor of PVSRIPO) has a financial interest in Istari Oncology, Inc., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule., Methods: This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at -10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference.. Safety was assessed as serious adverse events and important medical events. This study is registered on ClinicalTrials.gov, NCT03239496., Findings: From Oct 23, 2017, to Nov 13, 2018, we enrolled 773 infants (372 [48%] girls) in Panama and the Dominican Republic (two f-IPV group n=217, three f-IPV group n=178, two IPV group n=178, and three IPV group n=200). 686 infants received all scheduled vaccine doses and were included in the per-protocol analysis. We observed non-inferiority for poliovirus type 1 seroconversion rate at 40 weeks for the two f-IPV dose schedule (95·9% [95% CI 92·0-98·2]) versus the two IPV dose schedule (98·7% [95·4-99·8]), and for the three f-IPV dose schedule (98·8% [95·6-99·8]) versus the three IPV dose schedule (100% [97·9-100]). Similarly, poliovirus type 2 seroconversion rate at 40 weeks for the two f-IPV dose schedule (97·9% [94·8-99·4]) versus the two IPV dose schedule (99·4% [96·4-100]), and for the three f-IPV dose schedule (100% [97·7-100]) versus the three IPV dose schedule (100% [97·9-100]) were non-inferior. Seroconversion rate for the two f-IPV regimen was statistically superior 4 weeks after the last vaccine dose in the 14 and 36 week schedule (95·9% [92·0-98·2]) compared with the 10 and 14 week schedule (83·2% [76·5-88·6]; p=0·0062) for poliovirus type 1. Statistical superiority of the 14 and 36 week schedule was also found for poliovirus type 2 (14 and 36 week schedule 97·9% [94·8-99·4] vs 10 and 14 week schedule 83·9% [77·2-89·2]; p=0·0062), and poliovirus type 3 (14 and 36 week schedule 84·5% [78·7-89·3] vs 10 and 14 week schedule 73·3% [65·8-79·9]; p=0·0062). For IPV, a two dose regimen administered at 14 and 36 weeks (99·4% [96·4-100]) was superior a 10 and 14 week schedule (88·9% [83·4-93·1]; p<0·0001) for poliovirus type 2, but not for type 1 (14 and 36 week schedule 98·7% [95·4-99·8] vs 10 and 14 week schedule 95·6% [91·4-98·1]), or type 3 (14 and 36 week schedule 97·4% [93·5-99·3] vs 10 and 14 week schedule 93·9% [89·3-96·9]). There were no related serious adverse events or important medical events reported in any group showing safety was unaffected by administration route or schedule., Interpretation: Our observations suggest that adequate immunity against poliovirus type 1 and type 2 is provided by two doses of either IPV or f-IPV at 14 and 36 weeks of age, and broad immunity is provided with three doses of f-IPV, enabling substantial savings in cost and supply. These novel clinical data will inform global polio immunisation policy for the post-eradication era., Funding: Bill & Melinda Gates Foundation., (Copyright © 2021 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.)

This report is an overview of enterovirus (EV) detection in Tunisian polio-suspected paralytic cases (acute flaccid paralysis (AFP) cases), healthy contacts and patients with primary immunodeficiencies (PID) during an 11-year period. A total of 2735 clinical samples were analyzed for EV isolation and type identification, according to the recommended protocols of the World Health Organization. Three poliovirus (PV) serotypes and 28 different nonpolio enteroviruses (NPEVs) were detected. The NPEV detection rate was 4.3%, 2.8% and 12.4% in AFP cases, healthy contacts and PID patients, respectively. The predominant species was EV-B, and the circulation of viruses from species EV-A was noted since 2011. All PVs detected were of Sabin origin. The PV detection rate was higher in PID patients compared to AFP cases and contacts (6.8%, 1.5% and 1.3% respectively). PV2 was not detected since 2015. Using nucleotide sequencing of the entire VP1 region, 61 strains were characterized as Sabin-like. Among them, six strains of types 1 and 3 PV were identified as pre-vaccine-derived polioviruses (VDPVs). Five type 2 PV, four strains belonging to type 1 PV and two strains belonging to type 3 PV, were classified as iVDPVs. The data presented provide a comprehensive picture of EVs circulating in Tunisia over an 11-year period, reveal changes in their epidemiology as compared to previous studies and highlight the need to set up a warning system to avoid unnoticed PVs.

Objective: To describe the prevalence of neutralizing antibodies against poliovirus (PV1, PV2, and PV3) in blood samples of healthcare professionals aged 20 to 50 years., Methods: Health professionals who serve children at Darcy Vargas Children's Hospital and the Department of Pediatrics of Irmandade da Santa Casa de São Paulo. The sample size was calculated at 323 participants. The Mantel-Haenszel chi-square was used to verify differences between groups. The neutralization reaction detected human poliovirus antibodies. For susceptible individuals, vaccination with the inactivated+triple acellular polio vaccine was performed, and neutralizing antibodies were re-dosed after one week., Results: 333 professionals were studied - 92.8% were immune to poliovirus 1, 86.5% to poliovirus 2, and 63.3% to poliovirus 3; 37% had titers less than 1:8 for any serotype, 5;1% had titers below 1:8 for all three. Vaccination with inactivated polio vaccine was performed for susceptible participants, and neutralizing antibodies were dosed after one week, showing increased titers for all polioviruses., Conclusions: Despite the detection of a significant percentage of individuals with low poliovirus antibody titer, the challenge with vaccination demonstrated immune response compatible with poliovirus immunity.

Many countries use supplemental immunization activities (SIAs) with oral poliovirus vaccine (OPV) to keep their population immunity to transmission high using preventive, planned SIAs (pSIAs) and outbreaks response SIAs (oSIAs). Prior studies suggested that investment in pSIAs saved substantial health and financial costs due to avoided outbreaks. However, questions remain about the benefits of SIAs, particularly with the recent introduction of inactivated poliovirus vaccine (IPV) into routine immunization in all OPV-using countries. The mounting costs of polio eradication activities and the need to respond to oSIAs threatens the use of limited financial resources for pSIAs, including in the remaining countries with endemic transmission of serotype 1 wild poliovirus (WPV1) (i.e., Pakistan and Afghanistan). A recent updated global poliovirus transmission model suggested that the Global Polio Eradication Initiative (GPEI) is not on track to stop transmission of WPV1 in Pakistan and Afghanistan. We use the updated global model to explore the role of pSIAs to achieve WPV1 eradication. We find that unless Pakistan and Afghanistan manage to increase the quality of bivalent OPV (bOPV) pSIAs, which we model as intensity (i.e., sufficiently high-coverage bOPV pSIAs that reach missed children), the model does not lead to successful eradication of WPV1. Achieving WPV1 eradication, the global objectives of the GPEI, and a successful polio endgame depend on effective and sufficient use of OPV. IPV use plays a negligible role in stopping transmission in Pakistan and Afghanistan and most other countries supported by the GPEI, and more IPV use will not help to stop transmission., (© 2020 Society for Risk Analysis.)

Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated poliovirus vaccine (IPV). With the Global Polio Eradication Initiative (GPEI) continuing to extend its timeline for ending the transmission of all wild polioviruses and to introduce new poliovirus vaccines, the polio vaccine supply chain continues to expand in complexity. The increased complexity leads to significant uncertainty about supply and costs. Notably, the strategy of phased OPV cessation of all three serotypes to stop all future incidence of poliomyelitis depends on successfully stopping the transmission of all wild polioviruses. Countries also face challenges associated with responding to any outbreaks that occur after OPV cessation, because stopping transmission of such outbreaks requires reintroducing the use of the stopped OPV in most countries. National immunization program leaders will likely consider differences in their risks and willingness-to-pay for risk reduction as they evaluate their investments in current and future polio vaccination. Information about the costs and benefits of future poliovirus vaccines, and discussion of the complex situation that currently exists, should prove useful to national, regional, and global decisionmakers and support health economic modeling. Delays in achieving polio eradication combined with increasing costs of poliovirus vaccines continue to increase financial risks for the GPEI., (© 2020 The Authors. Risk Analysis published by Wiley Periodicals LLC on behalf of Society for Risk Analysis.)

Nearly 20 years after the year 2000 target for global wild poliovirus (WPV) eradication, live polioviruses continue to circulate with all three serotypes posing challenges for the polio endgame. We updated a global differential equation-based poliovirus transmission and stochastic risk model to include programmatic and epidemiological experience through January 2020. We used the model to explore the likely dynamics of poliovirus transmission for 2019-2023, which coincides with a new Global Polio Eradication Initiative Strategic Plan. The model stratifies the global population into 72 blocks, each containing 10 subpopulations of approximately 10.7 million people. Exported viruses go into subpopulations within the same block and within groups of blocks that represent large preferentially mixing geographical areas (e.g., continents). We assign representative World Bank income levels to the blocks along with polio immunization and transmission assumptions, which capture some of the heterogeneity across countries while still focusing on global poliovirus transmission dynamics. We also updated estimates of reintroduction risks using available evidence. The updated model characterizes transmission dynamics and resulting polio cases consistent with the evidence through 2019. Based on recent epidemiological experience and prospective immunization assumptions for the 2019-2023 Strategic Plan, the updated model does not show successful eradication of serotype 1 WPV by 2023 or successful cessation of oral poliovirus vaccine serotype 2-related viruses., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Delays in achieving the global eradication of wild poliovirus transmission continue to postpone subsequent cessation of all oral poliovirus vaccine (OPV) use. Countries must stop OPV use to end all cases of poliomyelitis, including vaccine-associated paralytic polio (VAPP) and cases caused by vaccine-derived polioviruses (VDPVs). The Global Polio Eradication Initiative (GPEI) coordinated global cessation of all type 2 OPV (OPV2) use in routine immunization in 2016 but did not successfully end the transmission of type 2 VDPVs (VDPV2s), and consequently continues to use type 2 OPV (OPV2) for outbreak response activities. Using an updated global poliovirus transmission and OPV evolution model, we characterize outbreak response options for 2019-2029 related to responding to VDPV2 outbreaks with a genetically stabilized novel OPV (nOPV2) strain or with the currently licensed monovalent OPV2 (mOPV2). Given uncertainties about the properties of nOPV2, we model different assumptions that appear consistent with the evidence on nOPV2 to date. Using nOPV2 to respond to detected cases may reduce the expected VDPV and VAPP cases and the risk of needing to restart OPV2 use in routine immunization compared to mOPV2 use for outbreak response. The actual properties, availability, and use of nOPV2 will determine its effects on type 2 poliovirus transmission in populations. Even with optimal nOPV2 performance, countries and the GPEI would still likely need to restart OPV2 use in routine immunization in OPV-using countries if operational improvements in outbreak response to stop the transmission of cVDPV2s are not implemented effectively., (© 2020 Society for Risk Analysis.)

The emergence of circulating vaccine-derived polioviruses through evolution of the oral polio vaccine (OPV) poses a significant obstacle to polio eradication. Understanding the early genetic changes that occur as OPV evolves and transmits is important for preventing future outbreaks. Here, we use deep sequencing to define the evolutionary trajectories of type 2 OPV in a vaccine trial. By sequencing 497 longitudinal stool samples from 271 OPV2 recipients and household contacts, we were able to examine the extent of convergent evolution in vaccinated individuals and the amount of viral diversity that is transmitted. In addition to rapid reversion of key attenuating mutations, we identify strong selection at 19 sites across the genome. We find that a tight transmission bottleneck limits the onward transmission of these early adaptive mutations. Our results highlight the distinct evolutionary dynamics of live attenuated virus vaccines and have important implications for the success of next-generation OPV., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: China implemented the globally synchronized switch from trivalent oral poliovirus vaccine (tOPV) to bivalent OPV (bOPV) and introduced 1 dose of inactivated poliovirus vaccine on 1 May 2016. We assessed the impact of the switch on the immunity level against poliovirus, especially type 2., Methods: Children born between 2014 and 2017, who were brought to the hospitals in Urumqi city, Xinjiang Province in 2017, were enrolled and blood samples were collected to test for antibody titers against poliovirus. A comparison of seroprevalence between the children born before (preswitch group) and after the switch (postswitch group) was performed to assess the impact of the switch on the immunity level against polio., Results: A total of 172 subjects were enrolled. The overall seroprevalences were 98.8%, 79.1%, and 98.3% for types 1, 2, and 3, respectively. Seroprevalence for type 2 significantly decreased from 91.6% in the preswitch group to 67.4% in the postswitch group, but no statistically significant change was observed for both types 1 and 3., Conclusions: The switch from tOPV to bOPV can provide high-level immunity against types 1 and 3 but not against type 2, indicating a high risk of type 2 vaccine-derived poliovirus emergence and transmission., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Two novel type 2 oral poliovirus vaccine (OPV2) candidates, novel OPV2-c1 and novel OPV2-c2, designed to be more genetically stable than the licensed Sabin monovalent OPV2, have been developed to respond to ongoing polio outbreaks due to circulating vaccine-derived type 2 polioviruses., Methods: We did two randomised studies at two centres in Belgium. The first was a phase 4 historical control study of monovalent OPV2 in Antwerp, done before global withdrawal of OPV2, and the second was a phase 2 study in Antwerp and Ghent with novel OPV2-c1 and novel OPV2-c2. Eligible participants were healthy adults aged 18-50 years with documented history of at least three polio vaccinations, including OPV in the phase 4 study and either OPV or inactivated poliovirus vaccine (IPV) in the novel OPV2 phase 2 study, with no dose within 12 months of study start. In the historical control trial, participants were randomly assigned to either one dose or two doses of monovalent OPV2. In the novel OPV2 trial, participants with previous OPV vaccinations were randomly assigned to either one or two doses of novel OPV2-c1 or to one or two doses of novel OPV2-c2. IPV-vaccinated participants were randomly assigned to receive two doses of either novel OPV2-c1, novel OPV2-c2, or placebo. Vaccine administrators were unmasked to treatment; medical staff performing safety and reactogenicity assessments or blood draws for immunogenicity assessments were masked. Participants received the first vaccine dose on day 0, and a second dose on day 28 if assigned to receive a second dose. Primary objectives were assessments and comparisons of safety up to 28 days after each dose, including solicited adverse events and serious adverse events, and immunogenicity (seroprotection rates on day 28 after the first vaccine dose) between monovalent OPV2 and the two novel OPV2 candidates. Primary immunogenicity analyses were done in the per-protocol population. Safety was assessed in the total vaccinated population-ie, all participants who received at least one dose of their assigned vaccine. The phase 4 control study is registered with EudraCT (2015-003325-33) and the phase 2 novel OPV2 study is registered with EudraCT (2018-001684-22) and ClinicalTrials.gov (NCT04544787)., Findings: In the historical control study, between Jan 25 and March 18, 2016, 100 volunteers were enrolled and randomly assigned to receive one or two doses of monovalent OPV2 (n=50 in each group). In the novel OPV2 study, between Oct 15, 2018, and Feb 27, 2019, 200 previously OPV-vaccinated volunteers were assigned to the four groups to receive one or two doses of novel OPV2-c1 or novel OPV2-c2 (n=50 per group); a further 50 participants, previously vaccinated with IPV, were assigned to novel OPV2-c1 (n=17), novel OPV2-c2 (n=16), or placebo (n=17). All participants received the first dose of assigned vaccine or placebo and were included in the total vaccinated population. All vaccines appeared safe; no definitely vaccine-related withdrawals or serious adverse events were reported. After first doses in previously OPV-vaccinated participants, 62 (62%) of 100 monovalent OPV2 recipients, 71 (71%) of 100 recipients of novel OPV2-c1, and 74 (74%) of 100 recipients of novel OPV2-c2 reported solicited systemic adverse events, four (monovalent OPV2), three (novel OPV2-c1), and two (novel OPV2-c2) of which were considered severe. In IPV-vaccinated participants, solicited adverse events occurred in 16 (94%) of 17 who received novel OPV2-c1 (including one severe) and 13 (81%) of 16 who received novel OPV2-c2 (including one severe), compared with 15 (88%) of 17 placebo recipients (including two severe). In previously OPV-vaccinated participants, 286 (97%) of 296 were seropositive at baseline; after one dose, 100% of novel OPV2 vaccinees and 97 (97%) of monovalent OPV2 vaccinees were seropositive., Interpretation: Novel OPV2 candidates were as safe, well tolerated, and immunogenic as monovalent OPV2 in previously OPV-vaccinated and IPV-vaccinated adults. These data supported the further assessment of the vaccine candidates in children and infants., Funding: University of Antwerp and Bill & Melinda Gates Foundation., (Copyright © 2020 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: Continued emergence and spread of circulating vaccine-derived type 2 polioviruses and vaccine-associated paralytic poliomyelitis from Sabin oral poliovirus vaccines (OPVs) has stimulated development of two novel type 2 OPV candidates (OPV2-c1 and OPV2-c2) designed to have similar immunogenicity, improved genetic stability, and less potential to reacquire neurovirulence. We aimed to assess safety and immunogenicity of the two novel OPV candidates compared with a monovalent Sabin OPV in children and infants., Methods: We did two single-centre, multi-site, partly-masked, randomised trials in healthy cohorts of children (aged 1-4 years) and infants (aged 18-22 weeks) in Panama: a control phase 4 study with monovalent Sabin OPV2 before global cessation of monovalent OPV2 use, and a phase 2 study with low and high doses of two novel OPV2 candidates. All participants received one OPV2 vaccination and subsets received two doses 28 days apart. Parents reported solicited and unsolicited adverse events. Type 2 poliovirus neutralising antibodies were measured at days 0, 7, 28, and 56, and stool viral shedding was assessed up to 28 days post-vaccination. Primary objectives were to assess safety in all participants and non-inferiority of novel OPV2 day 28 seroprotection versus monovalent OPV2 in infants (non-inferiority margin 10%). These studies were registered with ClinicalTrials.gov, NCT02521974 and NCT03554798., Findings: The control study took place between Oct 23, 2015, and April 29, 2016, and the subsequent phase 2 study between Sept 19, 2018, and Sept 30, 2019. 150 children (50 in the control study and 100 of 129 assessed for eligibility in the novel OPV2 study) and 684 infants (110 of 114 assessed for eligibility in the control study and 574 of 684 assessed for eligibility in the novel OPV2 study) were enrolled and received at least one study vaccination. Vaccinations were safe and well tolerated with no causally associated serious adverse events or important medical events in any group. Solicited and unsolicited adverse events were overwhelmingly mild or moderate irrespective of vaccine or dose. Nearly all children were seroprotected at baseline, indicating high baseline immunity. In children, the seroprotection rate 28 days after one dose was 100% for monovalent OPV2 and both novel OPV2 candidates. In infants at day 28, 91 (94% [95% CI 87-98]) of 97 were seroprotected after receiving monovalent OPV2, 134 (94% [88-97]) of 143 after high-dose novel OPV2-c1, 122 (93% [87-97]) of 131 after low-dose novel OPV2-c1, 138 (95% [90-98]) of 146 after high-dose novel OPV2-c2, and 115 (91% [84-95]) of 127 after low-dose novel OPV2-c2. Non-inferiority was shown for low-dose and high-dose novel OPV2-c1 and high-dose novel OPV2-c2 despite monovalent OPV2 recipients having higher baseline immunity., Interpretation: Both novel OPV2 candidates were safe, well tolerated, and immunogenic in children and infants. Novel OPV2 could be an important addition to our resources against poliovirus given the current epidemiological situation., Funding: Fighting Infectious Diseases in Emerging Countries and Bill & Melinda Gates Foundation., (Copyright © 2020 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.)

Introduction: inspite of the demonstrable evidence of the preventive and protective ability of vaccines to reduce the outbreak of vaccine-preventable diseases, there are still some significant disease outbreaks recorded in our communities. In some settings, these outbreaks have been linked with poor vaccine management. Therefore, this study was conducted to compare the cold chain practices in Oyo State, Nigeria., Methods: we conducted a cross-sectional survey among health workers in the local government areas of Oyo State between October and November 2019. Using purposive sampling, we recruited all the 84 routine immunization focal persons for the study. A self-administered questionnaire was used to collect data on cold chain management. Data were analyzed using SPSS version 24 and bivariate analysis was done using Chi-square. Statistical significance was set at p < 0.05., Results: the mean age of the respondents was 46.4 ± 6.7 years. Most prevalent cadre in the rural facilities was health assistants (87.5%) while Community Extension Health Workers (54.8%) were prevalent in the urban (p = 0.002). The proportion of respondents with adequate cold chain equipment was significantly higher in the urban compared with the rural area. The cold boxes were the only adequate cold chain equipment found in the rural health facilities compared with the urban (p = 0.036)., Conclusion: there was a low proportion of qualified health workers and inadequate cold chain equipment in the rural area compared with the urban facilities. Engagement of skilled health workers and supply of the cold chain equipment are recommended., Competing Interests: The authors declare no competing interests., (Copyright: Olaniyan Akintunde Babatunde et al.)

One of the milestones of vaccinology is the depletion of the global impact of Poliomyelitis. The current vaccines to deal with Polio comprise the Sabin and Salk formulations. The main limitation of the former is the use of attenuated viruses that can revert into pathogenic forms, whereas the latter is more expensive and induces no protection in the intestinal tract; the site of virus replication. Genetically engineered plants cope with such limitations. In addition, they offer a low-cost alternative for production, storage and delivery of vaccines. This technology has been narrowly applied in the development of Polio vaccines. Herein, we explored the ability of tobacco cells to express the immunogenic VP1, VP2, VP3, and VP4 Polio antigens, which are relevant for vaccine development. Evidence on the expression of the plant-made Polio VPs is presented and an immunogenicity assessment proved their capacity to induce local and systemic humoral responses when administered by subcutaneous and oral routes. The plant-made VPs will be useful in the development of low-cost vaccine formulations able to induce effective mucosal immunity without the risks associated to the use of attenuated viruses; therefore there is a potential for this technology to contribute toward Polio eradication., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Dendritic cells (DCs) are pivotal stimulators of T cell responses. They provide essential signals (epitope presentation, proinflammatory cytokines, co-stimulation) to T cells and prime adaptive immunity. Therefore, they are paramount to immunization strategies geared to generate T cell immunity. The inflammatory signals DCs respond to, classically occur in the context of acute virus infection. Yet, enlisting viruses for engaging DCs is hampered by their penchant for targeting DCs with sophisticated immune evasive and suppressive ploys. In this review, we discuss our work on devising vectors based on a recombinant polio:rhinovirus chimera for effectively targeting and engaging DCs. We are juxtaposing this approach with commonly used, recently studied dsDNA virus vector platforms., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The potential role of enteric viral infections and the developing infant virome in affecting immune responses to the oral poliovirus vaccine (OPV) is unknown. Here we performed viral metagenomic sequencing on 3 serially collected stool samples from 30 Bangladeshi infants following OPV vaccination and compared findings to stool samples from 16 age-matched infants in the United States (US). In 14 Bangladeshi infants, available post-vaccination serum samples were tested for polio-neutralizing antibodies. The abundance (p = 0.006) and richness (p = 0.013) of the eukaryotic virome increased with age and were higher than seen in age-matched US infants (p < 0.001). In contrast, phage diversity metrics remained stable and were similar to those in US infants. Non-poliovirus eukaryotic virus abundance (3.68 log 10 vs. 2.25 log 10 , p = 0.002), particularly from potential viral pathogens (2.78log 10 vs. 0.83log 10 , p = 0.002), and richness (p = 0.016) were inversely associated with poliovirus shedding. Following vaccination, 28.6% of 14 infants tested developed neutralizing antibodies to all three Sabin types and also exhibited higher rates of poliovirus shedding (p = 0.020). No vaccine-derived poliovirus variants were detected. These results reveal an inverse association between eukaryotic virome abundance and poliovirus shedding. Overall gut virome ecology and concurrent viral infections may impact oral vaccine responsiveness in Bangladeshi infants.

Background: The globally synchronised introduction of inactivated poliovirus vaccine (IPV) and replacement of trivalent oral poliovirus vaccine (OPV) with bivalent OPV (bOPV) were successfully implemented in China's routine immunisation programme in May, 2016. In response to the global shortage of Salk-strain IPV, Sabin-strain IPV production was encouraged to develop and use in low-income and middle-income countries. We assessed the immunogenicity of the current routine poliovirus vaccination schedule in China and compared it with alternative schedules that use Sabin-strain IPV (sIPV) and bOPV., Methods: This open-label, randomised, controlled trial recruited healthy infants aged 60-75 days from two centres in Zhejiang, China. Eligible infants were full-term, due for their first polio vaccination, weighed more than 2·5 kg at birth, were healthy on physical examination with no obvious medical conditions, and had no contraindications to vaccination. Infants were randomly assigned (1:1:1) using permuted block randomisation (block size of 12) to one of three polio vaccination schedules, with the first, second, and third doses given at ages 2 months, 3 months, and 4 months, respectively: sIPV-bOPV-bOPV (1sIPV+2bOPV group; current regimen), sIPV-sIPV-bOPV (2sIPV+1bOPV group), or sIPV-sIPV-sIPV (3sIPV group). The primary endpoint was the proportion of infants with seroconversion to each of the three poliovirus serotypes 1 month after the third dose. Serious and medically important adverse events were monitored for up to 30 days after each vaccination. We assessed immunity in the per-protocol population (all children who completed all three vaccinations and had pre-vaccination and post-vaccination laboratory data) and safety in all children who received at least one dose of study vaccine. This trial is registered with Clinicaltrials.gov, NCT03147560., Results: Between May 1, 2016, and Dec 1, 2017, we enrolled and randomly assigned 528 eligible infants to one of the three treatment groups (176 in each group); 473 infants (158 in the 1sIPV+2bOPV group, 152 in the 2sIPV+1bOPV group, and 163 in the 3sIPV group) were included in the per-protocol population. 100% seroconversion against poliovirus types 1 and 3 was observed in all three groups. Infants who received an immunisation schedule containing bOPV had significantly higher antibody titres against poliovirus types 1 and 3 than did the sIPV-only group (2048 in all three treatment groups; p<0·0001). Seroconversion against type 2 poliovirus was observed in 98 (62%) infants in the 1sIPV+2bOPV group, 145 (95%) infants in the 2sIPV+1bOPV group, and 161 (99%) infants in the 3sIPV group. No serious adverse events occurred during the study; 14 minor, transient adverse events were observed, with no significant differences across study groups., Interpretation: All three study schedules were well tolerated and highly immunogenic against poliovirus types 1 and 3. Schedules containing two or three sIPV doses had higher seroconversion rates against poliovirus type 2 than did the schedule with a single dose of sIPV. Our findings support inclusion of two sIPV doses in the routine poliovirus vaccination schedule in China to provide better protection against poliovirus type 2 than provided by the current regimen., Funding: Chinese Center for Disease Control and Prevention and China National Biotec Group Company., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Maternal poliovirus antibodies could provide passive immunity to the newborns from poliovirus infection during their first few months of life, but they may impair the immune responses of infants to the poliovirus vaccine as well. In our study, we pooled the data from three clinical trials of the inactivated poliovirus vaccine (IPV) based on Sabin strains to investigate the effect of maternal poliovirus antibodies on the immune responses of infants to poliovirus vaccines., Methods: There were five groups in the pooled analysis, including low-dose Sabin IPV, medium-dose Sabin IPV, high-dose Sabin IPV, control Sabin IPV, and control Salk IPV groups. We reclassified the infants in different groups according to their maternal poliovirus antibodies by two methods, the first one included maternal antibody negative (< 1:8) and maternal antibody positive (≥1:8), and the second one included maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32. Then, we compared the geometric mean titers (GMTs), geometric mean antibody fold increases (GMIs) and seroconversion rates of poliovirus type-specific neutralizing antibodies after vaccination among participants with different maternal poliovirus antibody levels., Results: The GMTs and GMIs of three types of poliovirus antibodies after vaccination in maternal antibody negative participants were significantly higher than those in maternal antibody positive participants. The seroconversion rates of type II and type III poliovirus antibodies in maternal antibody positive participants were significantly lower than those in maternal antibody negative participants. Among participants with maternal antibody titer < 1:8, 1:8 ~ < 1:32 and ≥ 1:32, the GMTs and GMIs of three types of poliovirus antibodies after vaccination showed a tendency to decline with the increasing of maternal antibody levels. The seroconversion rates of three types of poliovirus antibodies in participants with maternal antibody titer ≥1:32 were significantly lower than those in participants with maternal antibody titer < 1:8 and 1:8 ~ < 1:32., Conclusions: Maternal poliovirus antibodies interfered with the immune responses of infants to poliovirus vaccines, and a high level of maternal antibodies exhibited a greater dampening effect., Trial Registration: ClinicalTrials.gov NCT04264598 February 11, 2020; ClinicalTrials.gov NCT04264546 February 11, 2020; ClinicalTrials.gov NCT03902054 April 3, 2019. Retrospectively registered.

Background: The poliovirus has been targeted for eradication since 1988. Kenya reported its last case of indigenous Wild Poliovirus (WPV) in 1984 but suffered from an outbreak of circulating Vaccine-derived Poliovirus type 2 (cVDPV2) in 2018. We aimed to describe Kenya's polio surveillance performance 2016-2018 using WHO recommended polio surveillance standards., Methods: Retrospective secondary data analysis was conducted using Kenyan AFP surveillance case-based database from 2016 to 2018. Analyses were carried out using Epi-Info statistical software (version 7) and mapping was done using Quantum Geographic Information System (GIS) (version 3.4.1)., Results: Kenya reported 1706 cases of AFP from 2016 to 2018. None of the cases were confirmed as poliomyelitis. However, 23 (1.35%) were classified as polio compatible. Children under 5 years accounted for 1085 (63.6%) cases, 937 (55.0%) cases were boys, and 1503 (88.1%) cases had received three or more doses of Oral Polio Vaccine (OPV). AFP detection rate substantially increased over the years; however, the prolonged health workers strike in 2017 negatively affected key surveillance activities. The mean Non-Polio (NP-AFP) rate during the study period was 2.87/ 100,000 children under 15 years, and two adequate specimens were collected for 1512 (88.6%) AFP cases. Cumulatively, 31 (66.0%) counties surpassed target for both WHO recommended AFP quality indicators., Conclusions: The performance of Kenya's AFP surveillance system surpassed the minimum WHO recommended targets for both non-polio AFP rate and stool adequacy during the period studied. In order to strengthen the country's polio free status, health worker's awareness on AFP surveillance and active case search should be strengthened in least performing counties to improve case detection. Similar analyses should be done at the sub-county level to uncover underperformance that might have been hidden by county level analysis.

Serums were collected from people to assess whether polio immunity level was high enough to satisfy the polio vaccine immunization switch in Chongqing.People in 7 age groups (<1 year, 1-2 years, 3-4 years, 5-6 years, 7-14 years, 15-19 years, ≧20 years) were randomly selected in 3 areas by different geographical features in 2015. Peripheral venous blood samples were obtained and assays to detect poliovirus (PV) -neutralizing antibodies were performed. Acute flaccid paralysis (AFP) data was collected from 2012 to 2016 in Chongqing to evaluate the performance of AFP surveillance system by indicator analysis.A total of 636 people were tested for PV neutralization antibodies (NA). Overall NA seroprevalence for PV1, PV2 and PV3 were 93.40%, 96.38% and 91.82%, and geometric mean titers (GMTs) were 61.14, 66.78 and 21.47, respectively. GMTs and NA seroprevalence for PV1, PV2 and PV3 in older people were lower than young people. There were significant differences in seroprevalences of PV1 and PV3 among geographic areas (P < .05) in Chongqing.High seroprevalence for PV1, PV2, and PV3 and qualified capability for monitoring AFP cases showed that the polio eradication program has made positive achievements in Chongqing and established a stable base for a polio vaccine immunization switch. Nevertheless, GMTs were negatively associated with age in the geographic districts with poor economical features, which will increase the risk of emergence of vaccine-derived PV after polio vaccine switch. More than 1 dose of inactivated polio vaccine should be introduced into the polio vaccine schedule, and the supplementary immunization of polio should still be annually carried out after polio vaccine switch, especially among elder children and the adults.

Design and application of epitope-based polyvalent vaccines have recently garnered attention as an efficient alternative for conventional vaccines. We previously have reported the in silico design of HHP antigen which encompasses the immune-dominant epitopes of Hepatitis B surface antigen (HBsAg), Hepatitis C core protein (HCVcp) and Poliovirus viral proteins (VPs). It has been shown that the HHP has desirable conformation to expose the epitopes, high antigenicity and other desired physicochemical and immunological properties. To confirm the accuracy of these predictions, the ex-vivo immunogenicity of the HHP was assessed. The HHP gene was chemically synthesized in pET28a and expressed in E. coli (BL21). The expressed protein was purified and its immunological potency was evaluated on dendritic cells (DCs) as antigen presenting cells (APCs). Functional analysis was assessed in co-cultivation of autologous T-cells with matured DCs (mDCs). T-cell activation, proliferation and cytokines secretion were evaluated using flowcytometry and ELISA methods. Our results indicated that the HHP could induce the DC maturation. The mDCs were able to trigger T-cell activation and proliferation. In silico design and ex-vivo confirmation of immunological potential could pave the way to introduce efficient immunogens for further analysis. The ability of HHP in DC maturation and T-cell activation makes it an amenable vaccine candidate for further in-vivo studies., 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. Published by Elsevier Inc.)

Although there have been no cases of serotype 2 wild poliovirus for more than 20 years, transmission of serotype 2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the serotype 2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all serotype 2 poliovirus. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimated the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. A novel OPV2, for which two candidates are currently in clinical trials, is urgently required, together with a contingency strategy if this vaccine does not materialize or perform as anticipated., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)