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Nature Jul 2023Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As...
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 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.
Topics: Animals; Mice; Disease Models, Animal; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Vaccines, Attenuated; Disease Eradication
PubMed: 37316671
DOI: 10.1038/s41586-023-06212-3 -
Human Vaccines & Immunotherapeutics Aug 2023Conflict poses a threat to the stability of health-care systems around the world. Within the context of immunization service delivery, conflict-affected geographies are... (Review)
Review
Conflict poses a threat to the stability of health-care systems around the world. Within the context of immunization service delivery, conflict-affected geographies are often dogged by recurrent disease outbreaks due to the inability to administer life-saving vaccines to children residing in these areas. Essential immunization coverage is often poor in conflict-affected geographies, and within the specific context of the Global Polio Eradication Initiative (GPEI), multiple rounds of supplementary immunization activities are often needed to compensate for the inability to provide adequate immunization services. In order to implement polio vaccination activities, GPEI has often resorted to innovative approaches to reach and vaccinate children in security-compromised areas. This article examines the approaches adopted by the global polio program in conducting vaccination activities in conflict-affected geographies with the aim of understanding how they have influenced the successes and setbacks of the program in its bid to eradicate all polioviruses.
Topics: Child; Humans; Animals; Dogs; Vaccination; Immunization; Behavior Therapy; Vaccination Coverage; Poliomyelitis
PubMed: 37489591
DOI: 10.1080/21645515.2023.2237390 -
MMWR. Morbidity and Mortality Weekly... Jan 2022Wild poliovirus types 2 and 3 were declared eradicated in 2015 and 2019, respectively, and, since 2017, transmission of wild poliovirus type 1 (WPV1) has been detected...
Wild poliovirus types 2 and 3 were declared eradicated in 2015 and 2019, respectively, and, since 2017, transmission of wild poliovirus type 1 (WPV1) has been detected only in Afghanistan and Pakistan. In 2020, these countries reported their highest number of WPV1 cases since 2014 and experienced outbreaks of type 2 circulating vaccine-derived poliovirus (cVDPV2)* (1); in Afghanistan, the number of WPV1 cases reported increased 93%, from 29 in 2019 to 56 in 2020, with 308 cVDPV2 cases reported. This report describes the activities and progress toward polio eradication in Afghanistan during January 2020-November 2021 and updates previous reports (2-4). Despite restrictions imposed by antigovernment elements since 2018, disruption of polio eradication efforts by the COVID-19 pandemic, and civil and political instability, eradication activities have resumed. During January-November 2021, four WPV1 cases and 43 cVDPV2 cases were detected, representing decreases of 93% from 56 and 85% from 281, respectively, during the same period in 2020. After the assumption of nationwide control by the current de facto government of Afghanistan during August 2021, health officials committed to oral poliovirus vaccine (OPV) campaigns nationwide, with the potential to vaccinate approximately 2.5 million children against poliovirus who were previously not accessible for ≥2 years. Although challenges remain, vigorous, sustained polio eradication efforts in Afghanistan could result in substantial progress toward eradication during 2022-2023.
Topics: Adult; Afghanistan; Child; Child, Preschool; Disease Eradication; Disease Outbreaks; Humans; Immunization Programs; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Surveillance
PubMed: 35051135
DOI: 10.15585/mmwr.mm7103a3 -
Revista Chilena de Infectologia :... Dec 2020Oral poliovirus vaccine (OPV) has been instrumental in controlling the polio epidemic, and stands out for its safety, efficacy, ease of oral administration, and low... (Review)
Review
Oral poliovirus vaccine (OPV) has been instrumental in controlling the polio epidemic, and stands out for its safety, efficacy, ease of oral administration, and low cost. However, despite these advantages, as it is a live attenuated virus vaccine, there is the possibility of mutations that confer neurovirulence. Therefore, surveillance for acute flaccid paralysis (AFP) is important, whether associated with live vaccines (VAPP) or vaccine-derived viruses (VDPV). In this review we present important data from Latin America in recent years, where data on VDPV of community transmission, of ambiguous origin and associated with immunodeficiencies are reviewed. Due to the presence of VDPV, it is important to strengthen the epidemiological surveillance system for AFP, with data much lower than those recommended in recent years in the Americas. Additionally, it is essential to improve vaccination coverage to reduce the number of infants at risk of acquiring poliomyelitis. Consequently, we present the vaccination coverage rates with the inactivated vaccine against poliovirus (IPV) in the region and analyze the vaccination programs against poliomyelitis in accordance with the recommendations of the Latin American Society of Pediatric Infectious Diseases (SLIPE; minimum 3 doses of IPV) and the WHO Strategic Advisory Expert Group (SAGE) on Immunization (minimum 2 doses of IPV). The study concludes with recommendations from the authors for the change from OPV to exclusive use of IPV, to increase vaccination coverage and to strengthen surveillance for AFP in the region.
Topics: Child; Humans; Immunization Schedule; Infant; Latin America; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Vaccination
PubMed: 33844811
DOI: 10.4067/S0716-10182020000600701 -
Risk Analysis : An Official Publication... Apr 2023Pakistan and Afghanistan pose risks for international transmission of polioviruses as the last global reservoir for wild poliovirus type 1 (WPV1) and a reservoir for...
Pakistan and Afghanistan pose risks for international transmission of polioviruses as the last global reservoir for wild poliovirus type 1 (WPV1) and a reservoir for type 2 circulating vaccine-derived polioviruses (cVDPV2s). Widespread transmission of WPV1 and cVDPV2 in 2019-2020 and resumption of intensive supplemental immunization activities (SIAs) in 2020-2021 using oral poliovirus vaccine (OPV) led to decreased transmission of WPV1 and cVDPV2 as of the end of 2021. Using an established dynamic disease transmission model, we explore multiple bounding scenarios with varying intensities of SIAs using bivalent OPV (bOPV) and/or trivalent tOPV (tOPV) to characterize potential die out of transmission. This analysis demonstrates potential sets of actions that may lead to elimination of poliovirus transmission in Pakistan and/or Afghanistan. Some modeled scenarios suggest that Pakistan and Afghanistan could increase population immunity to levels high enough to eliminate transmission, and if maintained, achieve WPV1 and cVDPV2 elimination as early as 2022. This requires intensive and proactive OPV SIAs to prevent transmission, instead of surveillance followed by reactive outbreak response. The reduction of cases observed in 2021 may lead to a false sense of security that polio has already or soon will die out on its own, but relaxation of immunization activities runs the risk of lowering population immunity to, or below, the minimum die-out threshold such that transmission continues. Transmission modeling may play a key role in managing expectations and supporting future modeling about the confidence of no virus circulation in anticipation of global certification decisions.
Topics: Humans; Poliovirus; Afghanistan; Pakistan; Poliovirus Vaccine, Oral; Poliomyelitis
PubMed: 35739080
DOI: 10.1111/risa.13983 -
Nature Communications Oct 2023Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of...
Global eradication of poliovirus remains elusive, and it is critical to develop next generation vaccines and antivirals. In support of this goal, we map the epitope of human monoclonal antibody 9H2 which is able to neutralize the three serotypes of poliovirus. Using cryo-EM we solve the near-atomic structures of 9H2 fragments (Fab) bound to capsids of poliovirus serotypes 1, 2, and 3. The Fab-virus complexes show that Fab interacts with the same binding mode for each serotype and at the same angle of interaction relative to the capsid surface. For each of the Fab-virus complexes, we find that the binding site overlaps with the poliovirus receptor (PVR) binding site and maps across and into a depression in the capsid called the canyon. No conformational changes to the capsid are induced by Fab binding for any complex. Competition binding experiments between 9H2 and PVR reveal that 9H2 impedes receptor binding. Thus, 9H2 outcompetes the receptor to neutralize poliovirus. The ability to neutralize all three serotypes, coupled with the critical importance of the conserved receptor binding site make 9H2 an attractive antiviral candidate for future development.
Topics: Humans; Serogroup; Antibodies, Monoclonal; Capsid Proteins; Poliovirus; Binding Sites; Antibodies, Viral
PubMed: 37816742
DOI: 10.1038/s41467-023-41052-9 -
Human Vaccines & Immunotherapeutics Feb 2021In 2000, China was declared polio-free. However, in 2018, wild poliovirus (WPV) was still endemic in two of its neighboring countries, making WPV importation and...
In 2000, China was declared polio-free. However, in 2018, wild poliovirus (WPV) was still endemic in two of its neighboring countries, making WPV importation and outbreak alarming possibilities. This study documents the seroprevalence of poliovirus antibodies before and after the polio vaccine switch in 2012 and 2017 in Beijing. Cross-sectional population-based serologic surveys were conducted in 2012 and 2017 in Beijing. The study subjects were selected from 10 different age groups (<1, 1-4, 5-9, 10-14, 15-19, 20-24, 25-29, 30-34, 35-39, and ≥40 y) using a multi-stage-stratified sampling method. Neutralizing antibody titers against poliovirus serotypes 1 (P1), 2 (P2), and 3 (P3) were assayed by World Health Organization standards. The seropositive rates (SR) and geometric mean titer (GMT) of the neutralizing antibodies were 91.71% and 1:130.26, respectively, for P1, 94.09% and 1:113.39, respectively, for P2, and 88.78% and 1:79.65, respectively, for P3 before the switch in 2012, and 87.78% and 1:108.93, respectively, for P1, and 81.67% and 1:70.56, respectively, for P3 after the switch in 2017, with a statistically significant difference for P1 and P3 between 2012 and 2017. The neutralizing antibodies for all poliovirus serotypes differed among different age and vaccination groups in both 2012 and 2017. After switching polio vaccines twice in 2014 and 2016, the P1 and P3 polio antibody levels were lower in 2017 than in 2012. The P2 antibody levels were determined from the first dose of IPV. The seroprevalence of poliovirus antibodies after adjustment of the immunization schedule of the polio vaccine on January 1, 2020, must be further monitored.
Topics: Antibodies, Viral; Beijing; China; Cross-Sectional Studies; Humans; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Seroepidemiologic Studies; Vaccination
PubMed: 32703060
DOI: 10.1080/21645515.2020.1778409 -
Risk Analysis : An Official Publication... Feb 2021Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated...
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.
Topics: Costs and Cost Analysis; Disease Eradication; Disease Outbreaks; Global Health; Health Care Costs; Humans; Immunization Programs; Models, Economic; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Risk; Risk Management; Serogroup; Vaccination
PubMed: 32645244
DOI: 10.1111/risa.13557 -
MMWR. Morbidity and Mortality Weekly... Apr 2022Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of reported poliomyelitis cases worldwide has declined by approximately 99.99%....
Since the Global Polio Eradication Initiative (GPEI) was established in 1988, the number of reported poliomyelitis cases worldwide has declined by approximately 99.99%. By the end of 2021, wild poliovirus (WPV) remained endemic in only two countries (Pakistan and Afghanistan). However, a WPV type 1 (WPV1) case with paralysis onset in 2021, was reported by Malawi a year after the World Health Organization (WHO) African Region (AFR) was certified as WPV-free and circulating vaccine-derived poliovirus (cVDPV) cases were reported from 31 countries during 2020-2021 (1,2). cVDPVs are oral poliovirus vaccine-derived viruses that can emerge after prolonged circulation in populations with low immunity and cause paralysis. The primary means of detecting poliovirus transmission is through surveillance for acute flaccid paralysis (AFP) among persons aged <15 years, with confirmation through stool specimen testing by WHO-accredited laboratories, supplemented by systematic sampling of sewage and testing for the presence of poliovirus (environmental surveillance). The COVID-19 pandemic caused disruptions in polio vaccination and surveillance activities across WHO regions in 2020; during January-September 2020, the number of reported cases of AFP declined and the interval between stool collection and receipt by laboratories increased compared with the same period in 2019 (3). This report summarizes surveillance performance indicators for 2020 and 2021 in 43 priority countries* and updates previous reports (4). In 2021, a total of 32 (74%) priority countries met two key surveillance performance indicator targets nationally, an improvement from 2020 when only 23 (53%) met both targets; however, substantial national and subnational gaps persist. High-performing poliovirus surveillance is critical to tracking poliovirus transmission. Frequent monitoring of surveillance indicators could help identify gaps, guide improvements, and enhance the overall sensitivity and timelines of poliovirus detection to successfully achieve polio eradication.
Topics: Humans; COVID-19; Disease Eradication; Global Health; Immunization Programs; Pandemics; Paralysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Surveillance
PubMed: 35421079
DOI: 10.15585/mmwr.mm7115a2 -
Risk Analysis : An Official Publication... Feb 2021Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency...
Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine-derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security-compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation-based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.
Topics: Child; Child, Preschool; Disease Outbreaks; Humans; Immunization Programs; Infant; Nigeria; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Risk Assessment; Vaccination
PubMed: 32348621
DOI: 10.1111/risa.13485