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MMWR. Morbidity and Mortality Weekly... Sep 2020Since 1988, when World Health Organization (WHO) Member States and partners launched the Global Polio Eradication Initiative, the number of wild poliovirus (WPV) cases...
Since 1988, when World Health Organization (WHO) Member States and partners launched the Global Polio Eradication Initiative, the number of wild poliovirus (WPV) cases has declined from 350,000 in 125 countries to 176 in only two countries in 2019 (1). The Global Commission for the Certification of Poliomyelitis Eradication (GCC) declared two of the three WPV types, type 2 (WPV2) and type 3 (WPV3), eradicated globally in 2015 and 2019, respectively (1). Wild poliovirus type 1 (WPV1) remains endemic in Afghanistan and Pakistan (1). Containment under strict biorisk management measures is vital to prevent reintroduction of eradicated polioviruses into communities from poliovirus facilities. In 2015, Member States committed to contain type 2 polioviruses (PV2) in poliovirus-essential facilities (PEFs) certified in accordance with a global standard (2). Member states agreed to report national PV2 inventories annually, destroy unneeded PV2 materials, and, if retaining PV2 materials, establish national authorities for containment (NACs) and a PEF auditing process. Since declaration of WPV3 eradication in October 2019, these activities are also required with WPV3 materials. Despite challenges faced during 2019-2020, including the coronavirus disease 2019 (COVID-19) pandemic, the global poliovirus containment program continues to work toward important milestones. To maintain progress, all WHO Member States are urged to adhere to the agreed containment resolutions, including officially establishing legally empowered NACs and submission of PEF Certificates of Participation.
Topics: Disease Eradication; Global Health; Humans; Poliomyelitis; Poliovirus Vaccine, Oral
PubMed: 32941411
DOI: 10.15585/mmwr.mm6937a7 -
Lancet (London, England) Jan 2023Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2)... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: a randomised, controlled, phase 2 clinical trial.
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.
Topics: Infant, Newborn; Humans; Infant; Child, Preschool; Bangladesh; Antibodies, Viral; Poliovirus Vaccine, Oral; Poliovirus; Poliomyelitis; Antibodies, Neutralizing; Double-Blind Method
PubMed: 36495882
DOI: 10.1016/S0140-6736(22)02397-2 -
Risk Analysis : An Official Publication... Feb 2021Nearly 20 years after the year 2000 target for global wild poliovirus (WPV) eradication, live polioviruses continue to circulate with all three serotypes posing...
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.
Topics: Disease Eradication; Disease Outbreaks; Global Health; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Risk Assessment; Risk Management; Vaccination
PubMed: 31960533
DOI: 10.1111/risa.13447 -
The Lancet. Microbe Dec 2022Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to...
Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials.
BACKGROUND
Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks.
METHODS
In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model.
FINDINGS
Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log 50% cell culture infectious dose (CCID) and 76·7% at the 5 log CCID inoculum levels, with rates of 2·8% for 4 log CCID and 11·8% for 5 log CCID observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients.
INTERPRETATION
The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Mice; Animals; Poliovirus; Poliomyelitis; Poliovirus Vaccine, Oral; 5' Untranslated Regions; Mice, Transgenic; Paralysis; Nucleotides
PubMed: 36332645
DOI: 10.1016/S2666-5247(22)00254-3 -
Journal of Hematology & Oncology Jun 2020Natural killer (NK) cells are powerful immune effectors, modulating their anti-tumor function through a balance activating and inhibitor ligands on their cell surface.... (Review)
Review
Natural killer (NK) cells are powerful immune effectors, modulating their anti-tumor function through a balance activating and inhibitor ligands on their cell surface. Though still emerging, cancer immunotherapies utilizing NK cells are proving promising as a modality for the treatment of a number of solid tumors, including glioblastoma (GBM) and other gliomas, but are often limited due to complex immunosuppression associated with the GBM tumor microenvironment which includes overexpression of inhibitory receptors on GBM cells. CD155, or poliovirus receptor (PVR), has recently emerged as a pro-tumorigenic antigen, overexpressed on GBM and contributing to increased GBM migration and aggressiveness. CD155 has also been established as an immunomodulatory receptor, able to both activate NK cells through interactions with CD226 (DNAM-1) and CD96 and inhibit them through interaction with TIGIT. However, NK cell TIGIT expression has been shown to be upregulated in cancer, establishing CD155 as a predominantly inhibitory receptor within the context of GBM and other solid tumors, and rendering it of interest as a potential target for antigen-specific NK cell-based immunotherapy. This review will explore the function of CD155 within GBM as it relates to tumor migration and NK cell immunoregulation, as well as pre-clinical and clinical targeting of CD155/TIGIT and the potential that this pathway holds for the development of emerging NK cell-based immunotherapies.
Topics: Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Antineoplastic Agents, Immunological; Cell Adhesion; Cell Movement; Glioblastoma; Humans; Immunotherapy; Killer Cells, Natural; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Oncolytic Virotherapy; Poliovirus; Reassortant Viruses; Receptors, Immunologic; Receptors, Virus; Rhinovirus; Tumor Microenvironment
PubMed: 32532329
DOI: 10.1186/s13045-020-00913-2 -
Viruses Jul 2021The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global... (Review)
Review
The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global polio eradication. However, polio outbreaks, mainly caused by type 2 circulating vaccine-derived poliovirus (cVDPV2), are increasing worldwide. Meanwhile, immunodeficiency-associated vaccine-derived poliovirus (iVDPV) is considered another risk factor during the final stage of global polio eradication. Patients with primary immunodeficiency diseases are associated with higher risks for long-term iVDPV infections. Although a limited number of chronic iVDPV excretors were reported, the recent identification of a chronic type 2 iVDPV (iVDPV2) excretor in the Philippines highlights the potential risk of inapparent iVDPV infection for expanding cVDPV outbreaks. Further research on the genetic characterizations and molecular evolution of iVDPV2, based on comprehensive iVDPV surveillance, will be critical for elucidating the remaining risk of iVDPV2 during the post-OPV era.
Topics: Disease Eradication; Disease Outbreaks; Evolution, Molecular; Global Health; Humans; Immunocompromised Host; Poliovirus; Poliovirus Vaccine, Oral; Primary Immunodeficiency Diseases; Vaccination
PubMed: 34372613
DOI: 10.3390/v13071407 -
Vaccine Apr 2023In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in...
In early 2020, the COVID-19 pandemic led to substantial disruptions in global activities. The disruptions also included intentional and unintentional reductions in health services, including immunization campaigns against the transmission of wild poliovirus (WPV) and persistent serotype 2 circulating vaccine-derived poliovirus (cVDPV2). Building on a recently updated global poliovirus transmission and Sabin-strain oral poliovirus vaccine (OPV) evolution model, we explored the implications of immunization disruption and restrictions of human interactions (i.e., population mixing) on the expected incidence of polio and on the resulting challenges faced by the Global Polio Eradication Initiative (GPEI). We demonstrate that with some resumption of activities in the fall of 2020 to respond to cVDPV2 outbreaks and full resumption on January 1, 2021 of all polio immunization activities to pre-COVID-19 levels, the GPEI could largely mitigate the impact of COVID-19 to the delays incurred. The relative importance of reduced mixing (leading to potentially decreased incidence) and reduced immunization (leading to potentially increased expected incidence) depends on the timing of the effects. Following resumption of immunization activities, the GPEI will likely face similar barriers to eradication of WPV and elimination of cVDPV2 as before COVID-19. The disruptions from the COVID-19 pandemic may further delay polio eradication due to indirect effects on vaccine and financial resources.
Topics: Humans; Pandemics; COVID-19; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Disease Outbreaks; Global Health; Disease Eradication
PubMed: 33962838
DOI: 10.1016/j.vaccine.2021.04.026 -
Vaccines Sep 2023The oral poliovirus vaccine (OPV) has been the mainstay of polio eradication, especially in low-income countries, and its use has eliminated wild poliovirus type 2....
The oral poliovirus vaccine (OPV) has been the mainstay of polio eradication, especially in low-income countries, and its use has eliminated wild poliovirus type 2. However, the inactivated poliovirus vaccine (IPV) is safer than OPV, as IPV protects against paralytic poliomyelitis without producing adverse reactions. The present study compared mucosal and humoral responses to poliovirus vaccines administered to previously OPV-immunized children to assess the immunity gap in children in areas of high poliovirus transmission. A cluster-randomized trial was implemented in three high-risk districts of Pakistan-Karachi, Kashmore, and Bajaur-from June 2013 to May 2014. This trial was community-oriented and included three arms, focusing on healthy children below five years of age. The study involved the randomization of 387 clusters, of which 360 were included in the final analysis. The control arm (A) received the routine polio program bivalent poliovirus vaccine (bOPV). The second arm (B) received additional interventions, including health camps providing routine vaccinations and preventive maternal and child health services. In addition to the interventions in arm B, the third arm (C) was also provided with IPV. Blood and stool samples were gathered from children to evaluate humoral and intestinal immunity. The highest levels of poliovirus type 1 serum antibodies were observed in Group C (IPV + OPV). The titers for poliovirus type 2 (P2) and poliovirus type 3 (P3) were noticeably higher in those who had received a routine OPV dose than in those who had not across all study groups and visits. Providing an IPV booster after at least two OPV doses could potentially fill immunity gaps in regions where OPV does not show high efficacy. However, IPV only marginally enhances humoral immunity and fails to offer intestinal immunity, which is critical to stop the infection and spread of live poliovirus in populations that have not been exposed before.
PubMed: 37766121
DOI: 10.3390/vaccines11091444 -
Journal of Virology Dec 2019Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of...
Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota. Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.
Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bacteria; Coxsackievirus Infections; Disease Models, Animal; Enterovirus; Enterovirus Infections; HeLa Cells; Humans; Male; Mice; Mice, Inbred C57BL; Microbiota; Picornaviridae; Poliovirus; Vancomycin; Virus Replication
PubMed: 31511379
DOI: 10.1128/JVI.01339-19 -
Bulletin of the World Health... May 2023Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by...
Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future.
Topics: Humans; Poliovirus; Poliomyelitis; India; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Population Surveillance
PubMed: 37131936
DOI: 10.2471/BLT.22.289066