Search

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.

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.)

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.)

To address the biosafety and biosecurity concerns related to the manufacture of inactivated polio vaccine (IPV), several manufacturers started producing it from attenuated Sabin strains. Slight immunological differences between wild and attenuated strains create a challenge for testing IPV potency, which is defined as the content of protective D-antigen determined in an ELISA test. Some ELISA reagents selected for testing conventional IPV made from wild strains (cIPV) may not be suitable for testing Sabin IPV (sIPV). This paper describes an ELISA procedure using human monoclonal antibodies selected to capture equally well both wild and attenuated strains of poliovirus. A unique monoclonal antibody neutralizing all three serotypes of poliovirus was used as the detection antibody. The method was shown to detect only D-antigen of both conventional and Sabin IPV and to be strictly serotype-specific. The method is highly sensitive and robust and produces linear results in a wide range of concentrations. We have also found that reference standards used for measuring potency of cIPV and sIPV must be made from respective vaccines. This makes it impossible to cross-calibrate potency reagents made from heterologous vaccine and requires the establishment of a new unit to measure potency of sIPV that is different from conventional D-antigen unit., (Published by Elsevier B.V.)

Objectives : Wild poliovirus (WPV) infection has been eliminated in Europe through mass immunization. Resettling refugees may lack immunity and importing WPV through refugees continues to cause concerns. Method : We performed a cross-sectional study to establish the prevalence of poliovirus immunity in children and adult refugees resettling in Aarhus, Denmark. Immunity was evaluated by antibody response for serotypes 1, 2, and 3. Results : The participants in this study counted a total of 475 children and adult refugees aged between 6 months and 76 years and 59% were males. The survey was conducted between 2014 and 2016. Among the refugees, 72% were from Syria, and the rest from Eritrea, Congo, Lebanon, Somalia, Afghanistan, Iran, Iraq, Ethiopia, and Columbia. In the cohort, 27 lacked antibodies against a least one serotype. None of the participants lacked antibodies against all three polio types. Originating from The Horn of Africa, age between 20 and 30 and male gender was associated with lack of immunity. Conclusion : The study found a complete WPV immunity in 94% of recently resettled refugees in Denmark. This study demonstrates a high coverage of the polio immunization program. However, ensuring poliovirus immunity among refugees remains a priority until polio has been eradicated worldwide.

Patients with immunodeficiency-associated vaccine-derived poliovirus (iVDPV) are potential poliovirus reservoirs in the posteradication era that might reintroduce polioviruses into the community. We update the iVDPV registry in Iran by reporting 9 new patients. In addition to national acute flaccid paralysis surveillance, cases were identified by screening nonparalyzed primary immunodeficiency (PID) patients. Overall, 23 iVDPV patients have been identified since 1995. Seven patients (30%) never had paralysis. Poliovirus screening accelerated the iVDPV detection rate in Iran after 2014.The iVDPV infection rate among nonparalyzed patients with adaptive PID was 3.1% (7/224), several folds higher than previous estimates. Severe combined immunodeficiency patients had the highest risk for asymptomatic infection (28.6%) compared with other PIDs. iVDPV2 emergence has decreased after the switch from trivalent to bivalent oral poliovirus vaccine in 2016. However, emergence of iVDPV1 and iVDPV3 continued. Poliovirus screening in PID patients is an essential step in the endgame of polio eradication.

Background: Polio eradication has been achieved in the world except for three countries due to the widespread use of the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine. Following polio eradication, the IPV would be the only polio vaccine available. However, the mechanisms of the interactions between IPV and human antigen-presenting cells (APCs) remain largely unclear., Methods: To investigate the involvement of the IPV in human monocytes, we downloaded the gene chip GSE44721 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R analysis tool. Functional and pathway enrichment analyses were performed for DEGs using the Metascape database. DEG-associated protein-protein-interactions (PPIs) were established by the Search Tool for the Retrieval of Interacting Genes website and visualized by Cytoscape., Results: There were 240 DEGs (51 upregulated and 189 downregulated genes) identified from the GSE44721 data set, and they were significantly enriched in several biological processes, including antigen processing and presentation of lipid antigen via MHC class Ib, adaptive immune response, and response to interferon-gamma. One hundred thirty-six nodes were screened from the DEG PPI network. There were six significant hub proteins (WDR36, MRTO4, RPF2, PPAN, CD40, and BMS1) that regulated the IPV in human monocytes., Conclusions: In summary, using bioinformatical analysis, we have information for the immunization activated by the IPV in monocytes. Moreover, hormones and cytokines regulate the activation of APCs., (© 2019 Wiley Periodicals, Inc.)

Beginning in 1974, the date on which the Expanded Program on Immunization was established in the Americas, the number of deaths and disabilities due to certain infectious diseases decreased considerably thanks to universally applied vaccines. A program that initially included four vaccines that protected against six diseases (tuberculosis, diphtheria, pertussis, tetanus, polio and measles) was consolidated, over the years, by incorporating new vaccines and significantly raising coverage rates. The Sociedad Argentina de Pediatría (Argentine Society of Pediatrics), as a leader of opinion, played a leading role in the incorporation of new vaccines, currently reaching one of the most complete vaccination calendars in the world, which improves the levels of inequality and inequity in public health. Taking into account the significant role of the pediatrician in decision-making, the National Committee of Infectious Diseases, together with the Subsidiary Committees, prepared a document on updates and recommendations for 2018 on Polio, Rotavirus, Pneumococcus, Meningococcus, Human Papillomavirus, Chickenpox, Flu, Dengue vaccines and Whooping Cough., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Objective: To systematically review literature on uptake and timeliness of diphtheria-tetanus-pertussis, measles-mumps-rubella, and/or polio-containing vaccines ininfants who were born preterm, with a low birth weight, and/or with chronic health conditions that were diagnosed within the first 6 months of life., Methods: Using a standardized search strategy developed by a medical librarian, records were extracted from MEDLINE, Embase, Database of Abstracts of Reviews of Effects, and CINAHL up to May 8, 2018., Results: Out of the 1997 records that were screened, we identified 21 studies that met inclusion criteria. Eleven studies assessed vaccine coverage and/or timeliness in preterm infants, 6 in low birth weight infants, and 7 in children with chronic health conditions. Estimates of coverage in these populations were highly variable, ranging from 40% to 100% across the vaccines and population groups., Conclusions: There is a lack of studies reporting coverage and timeliness of routine immunizations in special populations of children., Policy Implications: Our review suggests a need for improved surveillance of immunization status in special populations of infants, as wellas aneed for standardization of reporting practices., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Since the launch of the Global Polio Eradication Initiative (GPEI), paralytic cases associated with wild poliovirus (WPV) have fallen from ∼350,000 in 1988 to 22 in 2017. WPV type 2 (WPV2) was last detected in 1999, WPV3 in 2012, and WPV1 appeared to be localized to Pakistan and Afghanistan in 2017. Through continuous refinement, the GPEI has overcome operational and biological challenges far more complex and daunting than originally envisioned. Operational challenges had led to sustained WPV endemicity in core reservoirs and widespread dissemination to polio-free countries. The biological challenges derive from intrinsic limitations to the oral poliovirus vaccine: ( a) reduced immunogenicity in high-risk settings and ( b) genetic instability, leading to repeated outbreaks of circulating vaccine-derived polioviruses and prolonged infections in individuals with primary immunodeficiencies. As polio eradication enters its multifaceted endgame, the GPEI, with its technical, operational, and social innovations, stands as the preeminent model for control of vaccine-preventable diseases worldwide.

The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe but expensive and does not induce the mucosal immunity necessary to interrupt virus transmission. While the need for a better vaccine is widely recognized, current efforts are focused largely on improvements to the OPV or IPV, which are still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of an antipoliovirus vaccine based on in situ production of virus-like particles (VLPs). The poliovirus capsid protein precursor, together with a protease required for its processing, are expressed from a Newcastle disease virus (NDV) vector, a negative-strand RNA virus with mucosal tropism. In this system, poliovirus VLPs are produced in the cells of vaccine recipients and are presented to their immune systems in the context of active replication of NDV, which serves as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody responses. Thus, the vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle. IMPORTANCE A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced in vivo , in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage., (Copyright © 2018 American Society for Microbiology.)

Objectives: To assess the prevalence of protective antibody titers to polioviruses in adults candidates for solid organ transplant (SOT), and to assess the immunogenic response to inactivated polio vaccine in this population., Methods: The study included SOT candidates referred to Immunization Reference Centre of Evandro Chagas National Institute of Infectious Diseases from March 2013 to January 2016. It was conducted in 2 phases. The first one, a cross-sectional seroprevalence study, followed by an uncontrolled analysis of vaccine response among patients without protective antibody titers at baseline. Antibody titers to poliomyelitis were determined by microneutralization assay., Results: Among 206 SOT candidates included, 156 (76%) had protective antibody titers to all poliovirus serotypes (95% CI: 70-81%). Proven history of oral vaccination in childhood was not associated with higher seroprevalence of protective antibody. In 97% of individuals without protective antibody titers at baseline, there was adequate vaccine response with one dose of inactivated polio vaccine., Conclusions: A relevant proportion of adult candidates for SOT does not have protective titers of antibodies to one or more poliovirus serotype. One dose of inactivated vaccine elicited protective antibody titers in 97% of these subjects and should be routinely prescribed prior to SOT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In vivo potency testing of inactivated poliovirus vaccines (IPV) is generally performed in rats, although no systematic investigation has identified the most appropriate rat strain for anti-poliovirus antibody quantification. We investigated humoral immune responses to IPV in five different rat strains to identify the most suitable strain. Three outbred (Wistar, Wistar Hannover, Sprague-Dawley) and two inbred rat strains (Fisher 344, Wistar Furth) were immunized intramuscularly with a full or one-fifth human dose of commercial IPV. Anti-poliovirus neutralizing antibody (NA) titers were measured using Salk and Sabin virus neutralizing assays. Post-vaccination responses varied between strains; inbred strains showed greater animal-to-animal variation in NA responses than outbred strains. Virus NA titers persisted for 9 weeks with little reduction in the response. The outbred Wistar rat model was identified as the preferred strain for IPV potency testing based on its capacity to produce high, dose-dependent anti-poliovirus NA responses, with low animal-to-animal variation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In 2015, several provinces in Lao People's Democratic Republic (Lao PDR) experienced a vaccine-derived poliovirus outbreak. This survey was conducted (i) to evaluate the vaccination coverage in different settings and cohorts using the seroprevalence of anti-poliovirus (PV) antibodies as a surrogate measure, and (ii) to explore the usefulness of an ELISA in a country with limited resources and a specific epidemiological setting. IgG antibodies were assessed by ELISA in Lao children (n = 1216) and adults (n = 1228), including blood donors and health care workers. Protective antibody titers against the 3 vaccine serotypes were determined by microneutralization (VNT) in a subset of participants. More than 92% of the children had anti-poliovirus antibodies, regardless of nutritional status or access to health care, highlighting the success of the vaccination outreach activities in the country. In contrast, anti-poliovirus seroprevalence reached only 81.7% in blood donors and 71.9% in health care workers. Participants born before the introduction of poliovirus vaccination in Lao PDR were considerably less likely to be seropositive. These findings align with the epidemiology of the outbreak. Neutralizing antibodies against at least one of the 3 poliovirus serotypes were detected in all children (99/99) and 93/99 had antibodies against all serotypes. Similarly, all health care workers had neutralizing antibodies against at least one and 92/99 against all serotypes. The comparison of both assays shows an acceptable underestimation of vaccine coverage in children by ELISA, but a low sensitivity of the ELISA in the adults. We show that the ELISA is a reasonable alternative to the VNT in particular in vaccinated children, that an improved version should be serotype specific, and that negativity thresholds should be revisited for optimal sensitivity and specificity. Thus, polio-free countries with an uncertain vaccination coverage and limited laboratory capacity, that are at risk of vaccine-derived poliovirus outbreaks or of re-importation of wild poliovirus may benefit from an improved ELISA for cohort studies to evaluate their immunization program in children.

The global adoption of vaccines to combat disease is hampered by the high cost of vaccine manufacturing. The work described herein follows two previous publications (van der Sanden et al., 2016; Wu et al., 2017) that report a strategy to enhance poliovirus and rotavirus vaccine production through genetic modification of the Vero cell lines used in large-scale vaccine manufacturing. CRISPR/Cas9 gene editing tools were used to knockout Vero target genes previously shown to play a role in polio- and rotavirus production. Subsequently, small-scale models of current industry manufacturing systems were developed and adopted to assess the increases in polio- and rotavirus output by multiple stable knockout cell lines. Unlike previous studies, the Vero knockout cell lines failed to achieve desired target yield increases. These findings suggest that additional research will be required before implementing the genetically engineered Vero cell lines in the manufacturing process for polio- and rotavirus vaccines to be able to supply vaccines at reduced prices., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Afghanistan is one of the remaining wild-poliovirus (WPV) endemic countries. We conducted a seroprevalence survey of anti-poliovirus antibodies in Kandahar Province., Methods: Children in two age groups (6-11 months and 36-48 months) visiting Mirwais hospital in Kandahar for minor ailments unrelated to polio were enrolled. After obtaining informed consent, we collected venous blood and conducted neutralization assay to detect poliovirus neutralizing antibodies., Results: A total of 420 children were enrolled and 409/420 (97%) were analysed. Seroprevalence to poliovirus type 1 (PV1) was 97% and 100% in the younger and older age groups respectively; it was 71% and 91% for PV2; 93% and 98% for PV3. Age group (RR = 3.6, CI 95% = 2.2-5.6) and place of residence outside of Kandahar city (RR = 1.8, CI 95% = 1.2-2.6) were found to be significant risk factors for seronegativity., Conclusions: The polio eradication program in Kandahar achieved high serological protection, especially against PV1 and PV3. Lower PV2 seroprevalence in the younger age group is a result of a withdrawal of live type 2 vaccine in 2016 and is expected. Ability to reach all children with poliovirus vaccines is a pre-requisite for achieving poliovirus eradication., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: During 2013, isolation of a wild type 1 poliovirus from routine sewage sample in Israel, led to a national OPV campaign. During this period, there was a constant cover of the outbreak by the mass media., Aims: To investigate the association of media exposure and OPV and non-OPV vaccines uptake during the 2013 silent polio outbreak in Israel., Methods: We received data on daily immunization rates during the outbreak period from the Ministry of Health (MoH). We conducted a multivariable time trend analysis to assess the association between daily media exposure and vaccines uptake. Analysis was stratified by ethnicity and socio-economic status (SES)., Results: During the MoH supplemental immunization activity, 138,799 OPV vaccines were given. There was a significant association between media exposure and OPV uptake, most prominent in a lag of 3-5 days from the exposure among Jews (R.R 1.79C.I 95% 1.32-2.41) and high SES subgroups (R.R 1.71C.I 95% 1.27-2.30). These subgroups also showed increased non-OPV uptake in a lag of 3-5 days from the media exposure, in all vaccines except for MMR. Lower SES and non-Jewish subgroups did not demonstrate the same association., Conclusion: Our findings expand the understanding of public behaviour during outbreaks. The public response shows high variability within specific subgroups. These findings highlight the importance of tailored communication strategies for each subgroup., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The goal of polio eradication is to complete elimination and containment of all wild, vaccine-related and Sabin polioviruses. Vaccine-derived poliovirus (VDPV) surveillance in China from 2001-2013 is summarized in this report, which has important implications for the global polio eradication initiative., Methods: Acute flaccid paralysis (AFP) cases and their contacts with VDPVs isolated from fecal specimens were identified in our AFP surveillance system or by field investigation. Epidemiological and laboratory information for these children were analyzed and the reasons for the VDPV outbreak was explored., Results: VDPVs were isolated from a total of 49 children in more than two-thirds of Chinese provinces from 2001-2013, including 15 VDPV cases, 15 non-polio AFP cases and 19 contacts of AFP cases or healthy subjects. A total of 3 circulating VDPVs (cVDPVs) outbreaks were reported in China, resulting in 6 cVDPVs cases who had not been vaccinated with oral attenuated poliomyelitis vaccine. Among the 4 immunodeficiency-associated VDPVs (iVDPVs) cases, the longest duration of virus excretion was about 20 months. In addition, one imported VDPV case from Myanmar was detected in Yunnan Province., Conclusions: Until all wild, vaccine-related and Sabin polioviruses are eradicated in the world, high quality routine immunization and sensitive AFP surveillance should be maintained, focusing efforts on underserved populations in high risk areas.

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.Despite the success of current vaccination against poliomyelitis, safe, cheap and effective vaccines remain sought for continuing eradication effort. Here the authors use plants to express stabilized virus-like particles of type 3 poliovirus that can induce a protective immune response in mice transgenic for the human poliovirus receptor.

Introduction: Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that require outbreak response using monovalent OPV (mOPV) and/or inactivated poliovirus vaccine. Areas covered: We review the experience and challenges with managing vaccine supplies in the context of the polio endgame. Building on models that explored polio endgame risks and the potential mOPV needs to stop outbreaks from live poliovirus reintroductions, we conceptually explore the potential demands for finished and bulk mOPV doses from a stockpile in the context of limited shelf-life of finished vaccine and time delays to convert bulk to finished vaccine. Our analysis suggests that the required size of the mOPV stockpile varies by serotype, with the highest expected needs for serotype 1 mOPV. Based on realizations of poliovirus risks after OPV cessation, the stockpile required to eliminate the chance of a stock-out appears considerably larger than the currently planned mOPV stockpiles. Expert commentary: The total required stockpile size depends on the acceptable probability of a stock-out, and increases with longer times to finish bulk doses and shorter shelf-lives of finished doses. Successful polio endgame management will require careful attention to poliovirus vaccine supplies.

Human cytomegalovirus (HCMV) infection drives the phenotypic and functional differentiation of NK cells, thereby influencing the responses of these cells after vaccination. NK cell functional differentiation is particularly advanced in African populations with universal exposure to HCMV. To investigate the impact of advanced differentiation on vaccine-induced responses, we studied NK-cell function before and after vaccination with Trivalent Influenza Vaccine (TIV) or diphtheria, tetanus, pertussis, inactivated poliovirus vaccine (DTPiP) in Africans with universal, lifelong HCMV exposure. In contrast to populations with lower prevalence of HCMV infection, no significant enhancement of NK-cell responses (IFN-γ, CD107a, CD25) occurred after in vitro re-stimulation of post-vaccination NK cells with TIV or DTPiP antigens compared to pre-vaccination baseline cells. However, both vaccinations resulted in higher frequencies of NK cells producing IFN-γ in response to exogenous IL-12 with IL-18, which persisted for up to 6 months. Enhanced cytokine responsiveness was restricted to less differentiated NK cells, with increased frequencies of IFN-γ + cells observed within CD56 bright CD57 - , CD56 dim CD57 - NKG2C - and CD56 dim CD57 - NKG2C + NK-cell subsets. These data suggest a common mechanism whereby different vaccines enhance NK cell IFN-γ function in HCMV infected donors and raise the potential for further exploitation of NK cell "pre-activation" to improve vaccine effectiveness., (© 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The antibody species that patrol in a patient's blood are an invaluable part of the immune system. While most of them shield us from life-threatening infections, some of them do harm in autoimmune diseases. If we knew exactly all the antigens that elicited all the antibody species within a group of patients, we could learn which ones correlate with immune protection, are irrelevant, or do harm. Here, we demonstrate an approach to this question: First, we use a plethora of phage-displayed peptides to identify many different serum antibody binding peptides. Next, we synthesize identified peptides in the array format and rescreen the serum used for phage panning to validate antibody binding peptides. Finally, we systematically vary the sequence of validated antibody binding peptides to identify those amino acids within the peptides that are crucial for binding "their" antibody species. The resulting immune fingerprints can then be used to trace them back to potential antigens. We investigated the serum of an individual in this pipeline, which led to the identification of 73 antibody fingerprints. Some fingerprints could be traced back to their most likely antigen, for example the immunodominant capsid protein VP1 of enteroviruses, most likely elicited by the ubiquitous poliovirus vaccination. Thus, with our approach, it is possible, to pinpoint those antibody species that correlate with a certain antigen, without any pre-information. This can help to unravel hitherto enigmatic diseases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer. However it is known that the Sabin vaccine strains are genetically unstable and can revert to a virulent transmissible form. A possible solution to the need for virus growth would be to generate empty viral capsids by recombinant technology, but hitherto such particles are so unstable as to be unusable. We report here the genetic manipulation of the virus to generate stable empty capsids for all three serotypes. The particles are shown to be extremely stable and to generate high levels of protective antibodies in animal models., Competing Interests: The authors have declared that no competing interests exist.

Background: Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools., Methods: In the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest-the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV-IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants., Findings: 210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (p<0·0001) and 53 of 87 infants receiving bOPV-IPV (p<0·0001). Mucosal type 2 neutralisation and type-specific IgA were noted primarily in response to tOPV. An inverse correlation was noted between virus shedding and both serum type 2 neutralisation at challenge (p<0·0001) and mucosal type 2 neutralisation at challenge (p<0·0001)., Interpretation: Mucosal type-2-specific antibodies can be measured in stool and develop in response to receipt of OPV type 2 either in the primary vaccine series or at challenge. These mucosal antibodies influence the amount of virus that is shed in an established infection., Funding: Bill & Melinda Gates Foundation., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

During 2013/14, Israel witnessed the silent reintroduction and sustained transmission of wild poliovirus type 1 (WPV1) detected through routine environmental surveillance performed on sewage samples. The public health response to silent poliovirus transmission in a population with high inactivated polio vaccine (IPV) coverage poses an emerging challenge towards the 'End Game' of global poliovirus eradication. This paper reviews the risk assessment, risk management and risk communication aspects of this poliovirus incident. Special emphasis is placed on the use of scientific data generated in the risk assessment phase to inform the public health response. Reintroducing a live vaccine in supplemental immunization activities in response to transmission of WPV or vaccine-derived poliovirus should be considered close to the 'End Game' of polio eradication, especially if targeting the population at risk is feasible. Such circumstances require a comprehensive contingency plan that will support the generation of important public health evidence at the risk assessment stage, thereby allowing to tailor the risk management approaches and underpin appropriate risk communication., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aim: To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response., Methods: INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management., Results: Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations., Conclusion: New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.

Background: Social media can act as an important platform for debating, discussing, and disseminating information about vaccines. Our objectives were to map and describe the roles played by web-based mainstream media and social media as platforms for vaccination-related public debates and discussions during the Polio crisis in Israel in 2013: where and how did the public debate and discuss the issue, and how can these debates and discussions be characterized?, Method: Polio-related coverage was collected from May 28 to October 31, 2013, from seven online Hebrew media platforms and the Facebook groups discussing the Polio vaccination were mapped and described. In addition, 2,289 items from the Facebook group "Parents talk about Polio vaccination" were analyzed for socio-demographic and thematic characteristics., Results: The traditional media mainly echoed formal voices from the Ministry of Health. The comments on the Facebook vaccination opposition groups could be divided into four groups: comments with individualistic perceptions, comments that expressed concerns about the safety of the OPV, comments that expressed distrust in the Ministry of Health, and comments denying Polio as a disease. In the Facebook group "Parents talk about the Polio vaccination", an active group with various participants, 321 commentators submitted 2289 comments, with 64 % of the comments written by women. Most (92 %) people involved were parents. The comments were both personal (referring to specific situations) and general in nature (referring to symptoms or wide implications). A few (13 %) of the commentators were physicians ( n  = 44), who were responsible for 909 (40 %) of the items in the sample. Half the doctors and 6 % of the non-doctors wrote over 10 items each. This Facebook group formed a unique platform where unmediated debates and discussions between the public and medical experts took place., Conclusion: The comments on the social media, as well as the socio-demographic profiles of the commentators, suggest that social media is an active and versatile debate and discussion-facilitating platform in the context of vaccinations. This paper presents public voices, which should be seen as authentic (i.e. unmediated by the media or other political actors) and useful for policy making purposes. The policy implications include identifying social media as a main channel of communication during health crises, and acknowledging the voices heard on social media as authentic and useful for policy making. Human and financial resources need to be devolved specifically to social media. Health officials and experts need to be accessible on social media, and be equipped to readily provide the information, support and advice the public is looking for.

The Global Polio Eradication Initiative (GPEI) has seen significant progress since it began in 1988, largely due to the worldwide use of oral poliovirus vaccine (OPV). In order to achieve polio eradication the global cessation of OPV is necessary because OPV contains live attenuated poliovirus, which in rare circumstances could re-gain wild poliovirus (WPV) characteristics with potential to establish transmission. The GPEI endgame strategy for the period 2013-2018 recommends the globally synchronised sequential cessation of the Sabin strains contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2 took place in April 2016, with the introduction of at least one dose of inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The introduction of IPV into 126 countries since 2013 has required a rapid scale-up of IPV production by the two manufacturers supplying the global public sector market. This scale-up has been fraught with challenges, resulting in reductions of 40-50% of initial supply commitments. Consequently, 22 countries will not be supplied until 2018, and another 23 countries will experience serious stock-outs. In the last decade repeated calls-for-action were made to the global community to invigorate their vision and investment in developing "new poliovirus vaccines" including the development of IPV from less-virulent strains, such as Sabin-IPV (S-IPV). The conventional Salk-IPV production is limited to high-income industrialized-country manufacturers due to the containment requirements (i.e., high sanitation, low force-of-poliovirus-infection, and high population immunity). The use of Sabin strains in the production of S-IPV carries a lower biosafety risk, and was determined to be suitable for production in developing countries, expanding the manufacturing base and making IPV more affordable and accessible in the long term. Significant progress in the S-IPV has been made since 2006. S-IPV is now licensed as S-IPV in Japan and as standalone S-IPV in China, demonstrating the feasibility of this vaccine. In addition, production process improvements can further reduce the cost of production. The latter are critical to the economic success of this vaccine in the global market. We summarize the progress made to date in S-IPV technology, the scientific data and economic evidence in support of S-IPV development., (Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Background: Vaccine schedules including bivalent oral and inactivated poliovirus vaccines will replace trivalent oral poliovirus vaccines in 2016., Methods: We evaluated rotavirus immunoglobulin A seroresponses when the second dose of Rotarix at 16 weeks was given concomitantly with inactivated or bivalent oral poliovirus vaccines., Results: Rotavirus immunoglobulin A seroresponse rate at week 28 was 15% lower in recipients of bivalent oral poliovirus vaccines compared with inactivated poliovirus vaccines., Conclusion: Bivalent oral poliovirus vaccine decreases rotavirus IgA seroresponse rates when coadministered at 16 weeks of age.

Rotavirus and poliovirus continue to present significant risks and burden of disease to children in developing countries. Developing a combined vaccine may effectively prevent both illnesses and may be advantageous in terms of maximizing compliance and vaccine coverage at the same visit. Recently, we sought to generate a vaccine vector by incorporating multiple epitopes into the rotavirus group antigenic protein, VP6. In the present study, a foreign epitope presenting a system using VP6 as a vector was created with six sites on the outer surface of the vector that could be used for insertion of foreign epitopes, and three VP6-based PV1 epitope chimeric proteins were constructed. The chimeric proteins were confirmed by immunoblot, immunofluorescence assay, and injected into guinea pigs to analyze the epitope-specific humoral response. Results showed that these chimeric proteins reacted with anti-VP6F and -PV1 antibodies, and elicited antibodies against both proteins in guinea pigs. Antibodies against the chimeric proteins carrying PV1 epitopes neutralized rotavirus Wa and PV1 infection in vitro. Our study contributes to a better understanding of the use of VP6-based vectors as multiple-epitope delivery vehicles and the epitopes displayed in this form could be considered for development of epitope-based vaccines against rotavirus and poliovirus.

Objective: To assess the seroprevalence against all three poliovirus serotypes in traditional high risk areas in Bihar, lowest routine immunization coverage areas in Madhya Pradesh and migrant population living in Mumbai urban slums., Design: Cross-sectional Survey., Setting: Subjects selected by house to house visit (community based) and transported to government health facilities for further study procedures., Participants: 1137 randomly selected healthy infants 6-11 months of age residing in the selected high-risk areas., Methods: Serum samples from the study site were shipped to Enterovirus Research Centre (ERC), Mumbai to determine the neutralizing antibodies against all three poliovirus serotypes. Children with a reciprocal antibody titer ≥1:8 were considered seropositive to the specific poliovirus., Results: Overall, seroprevalence in all the three study areas was 98%, 98% and 91% against poliovirus type-1, type-2 and type-3, respectively. Bihar had a seroprevalence of 99%, 99% and 92% against type-1, type-2 and type-3 respectively. Corresponding figures for Madhya Pradesh and Mumbai were 98%, 99% and 88% and 98%, 97% and 94%, respectively., Conclusion: The study found high seroprevalence against all three poliovirus types not only in the traditional high-risk areas for polio in India, but even in the areas known to have low routine immunization coverage and among the migratory clusters living in Mumbai urban slums. Type-2 seroprevalence was found to be high. These findings are reassuring against the threat of emergence of circulating vaccine derived polioviruses (cVDPVs) in the country subsequent to switch from trivalent oral polio vaccine to bivalent oral polio vaccine in the routine immunization schedule from April 2016.

To explore the genomic characterization of 4vaccine-derived poliovirus(VDPV)strains isolated from 2acute flaccid paralysis(AFP)cases in Yunnan Province in 2010 and 2012,respectively,the complete genome sequences of the 4strains were determined. Sequence analysis revealed that the complete genome length of the type Ⅱ and type Ⅰ VDPV was 7439nt and 7441 nt, respectively. Nucleotide and amino acid sequence similarities of type II VDPV were 95.4% and 97.7%,respectively,and type I VDPV were93.9% and 97.9%,respectively as compared with those of Sabin strains. Nucleotide substitutions were found at two important attenuation sites (nt 481 and nt in type Ⅱ VDPV, and three important attenuation sites(nt480,nt2795 and nt6203)in type I VDPV. Type 2 and type 1VDPV strains had 1.0% and2.3% divergence with Sabin strains, respectively. Similarity plot analysis showed multiple recombination events in the genome of the 4strains,which showed that the recombination was common and complex. Analysis of the characteristics of VDPVs on molecular level could provide valuable information on evolutionary dynamics and lay foundation for developing scientific and feasible strategy to control VDPV.

Recent polio outbreaks in Syria and Ukraine, and isolation of poliovirus from asymptomatic carriers in Israel have raised concerns that polio might endanger Europe. We devised a model to calculate the time needed to detect the first case should the disease be imported into Europe, taking the effect of vaccine coverage - both from inactivated and oral polio vaccines, also considering their differences - on the length of silent transmission into account by deriving an 'effective' case/infection ratio that is applicable for vaccinated populations. Using vaccine coverage data and the newly developed model, the relationship between this ratio and vaccine coverage is derived theoretically and is also numerically determined for European countries. This shows that unnoticed transmission is longer for countries with higher vaccine coverage and a higher proportion of IPV-vaccinated individuals among those vaccinated. Assuming borderline transmission (R = 1·1), the expected time to detect the first case is between 326 days and 512 days in different countries, with the number of infected individuals between 235 and 1439. Imperfect surveillance further increases these numbers, especially the number of infected until detection. While longer silent transmission does not increase the number of clinical diseases, it can make the application of traditional outbreak response methods more complicated, among others.

Background: Cases of paralysis caused by poliovirus have decreased by >99% since the 1988 World Health Assembly's resolution to eradicate polio. The World Health Organization identified environmental surveillance (ES) of poliovirus in the poliomyelitis eradication strategic plan as an activity that can complement acute flaccid paralysis (AFP) surveillance. This article summarizes key public health interventions that followed the isolation of polioviruses from ES between 2012 and 2015., Methods: The grap method was used to collect 1.75 L of raw flowing sewage every 2-4 weeks. Once collected, samples were shipped at 4 °C to a polio laboratory for concentration. ES data were then used to guide program implementation., Results: From 2012 to 2015, ES reported 97 circulating vaccine-derived polioviruses (cVDPV2) and 14 wild polioviruses. In 2014 alone, 54 cVDPV type 2 cases and 1 WPV type 1 case were reported. In Sokoto State, 58 cases of AFP were found from a search of 9426 households. A total of 2 252 059 inactivated polio vaccine and 2 460 124 oral polio vaccine doses were administered to children aged <5 year in Borno and Yobe states., Conclusions: This article is among the first from Africa that relates ES findings to key public health interventions (mass immunization campaigns, inactivated polio vaccine introduction, and strengthening of AFP surveillance) that have contributed to the interruption of poliovirus transmission in Nigeria., (© 2016 World Health Organization; licensee Oxford Journals.)

Background: The polio eradication initiative had major setbacks in 2003 and 2007 due to media campaigns in which renowned scholars and Islamic clerics criticized polio vaccines. The World Health Organization (WHO) partnered with journalists in 2007 to form the Journalists Initiatives on Immunisation Against Polio (JAP), to develop communication initiatives aimed at highlighting polio eradication activities and the importance of immunization in northern Nigeria., Methods: We evaluated the impact of JAP activities in Kaduna State by determining the total number of media materials produced and the number of newspaper clips and bulletins published in support of polio eradication. We also determined the number of households in noncompliant communities that became compliant with vaccination during 2015 supplementary immunization activities (SIAs) after JAP interventions and compared caregivers' sources of information about SIAs in 2007 before and after the JAP was formed., Results: Since creation of the JAP, >500 reports have been published and aired, with most portraying polio vaccine positively. During June 2015 SIAs in high-risk wards of Kaduna STATE, JAP interventions resulted in vaccination of 5122 of 5991 children (85.5%) from noncompliant households. During early 2007, the number of caregivers who had heard about SIA rounds from the media increased from 26% in January, before the JAP was formed, to 33% in March, after the initiation of JAP activities., Conclusions: The formation of the JAP resulted in measurable improvement in the acceptance of polio vaccine in northern Nigeria., (© 2016 World Health Organization; licensee Oxford Journals.)

Introduction: Poliomyelitis remains a global threat despite availability of oral polio vaccine (OPV), proven to reduce the burden of the paralyzing disease. In Nigeria, children continue to miss the opportunity to be fully vaccinated, owing to factors such as unmet health needs and low uptake in security-compromised and underserved communities. We describe the implementation and evaluation of several activities to create demand for polio vaccination in persistently poor-performing local government areas (LGAs)., Methods: We assessed the impact of various polio-related interventions, to measure the contribution of demand creation activities in 77 LGAs at very high risk for polio, located across 10 states in northern Nigeria. Interventions included provision of commodities along with the polio vaccine., Results: There was an increasing trend in the number of children reached by different demand creation interventions. A total of 4 819 847 children were vaccinated at health camps alone. There was a reduction in the number of wards in which >10% of children were missed by supplementary immunization activities due to noncompliance with vaccination recommendations, a rise in the proportion of children who received ≥4 OPV doses, and a decrease in the proportion of children who were underimmunized or unimmunized., Conclusions: Demand creation interventions increased the uptake of polio vaccines in persistently poor-performing high-risk communities in northern Nigeria during September 2013-November 2014., (© 2016 World Health Organization; licensee Oxford Journals.)

Introduction: Nigeria is among the 3 countries in which polio remains endemic. The country made significant efforts to reduce polio transmission but remains challenged by poor-quality campaigns and poor team performance in some areas. This article demonstrates the application of geographic information system technology to track vaccination teams to monitor settlement coverage, reduce the number of missed settlements, and improve team performance., Methods: In each local government area where tracking was conducted, global positioning system-enabled Android phones were given to each team on a daily basis and were used to record team tracks. These tracks were uploaded to a dashboard to show the level of coverage and identify areas missed by the teams., Results: From 2012 to June 2015, tracking covered 119 immunization days. A total of 1149 tracking activities were conducted. Of these, 681 (59%) were implemented in Kano state. There was an improvement in the geographic coverage of settlements and an overall reduction in the number of missed settlements., Conclusions: The tracking of vaccination teams provided significant feedback during polio campaigns and enabled supervisors to evaluate performance of vaccination teams. The reports supported other polio program activities, such as review of microplans and the deployment of other interventions, for increasing population immunity in northern Nigeria., (© 2016 World Health Organization; licensee Oxford Journals.)

The High-performance Integrated Virtual Environment (HIVE) is a distributed storage and compute environment designed primarily to handle next-generation sequencing (NGS) data. This multicomponent cloud infrastructure provides secure web access for authorized users to deposit, retrieve, annotate and compute on NGS data, and to analyse the outcomes using web interface visual environments appropriately built in collaboration with research and regulatory scientists and other end users. Unlike many massively parallel computing environments, HIVE uses a cloud control server which virtualizes services, not processes. It is both very robust and flexible due to the abstraction layer introduced between computational requests and operating system processes. The novel paradigm of moving computations to the data, instead of moving data to computational nodes, has proven to be significantly less taxing for both hardware and network infrastructure.The honeycomb data model developed for HIVE integrates metadata into an object-oriented model. Its distinction from other object-oriented databases is in the additional implementation of a unified application program interface to search, view and manipulate data of all types. This model simplifies the introduction of new data types, thereby minimizing the need for database restructuring and streamlining the development of new integrated information systems. The honeycomb model employs a highly secure hierarchical access control and permission system, allowing determination of data access privileges in a finely granular manner without flooding the security subsystem with a multiplicity of rules. HIVE infrastructure will allow engineers and scientists to perform NGS analysis in a manner that is both efficient and secure. HIVE is actively supported in public and private domains, and project collaborations are welcomed. Database URL: https://hive.biochemistry.gwu.edu., (© The Author(s) 2016. Published by Oxford University Press.)

Background: Designing effective public health campaigns in areas of armed conflict requires a nuanced understanding of how violence impacts the epidemiology of the disease in question., Methods: We examine the geographical relationship between violence (represented by the location of detonated Improvised Explosive Devices) and polio incidence by generating maps of IEDs and polio incidence during 2010, and by comparing the mean number of IED detonations in polio high-risk districts with non polio high-risk districts during 2004-2009., Results: We demonstrate a geographic relationship between IED violence and incident polio. Districts that have high-risk for polio have highly statistically significantly greater mean numbers of IEDs than non polio high-risk districts (p-values 0.0010-0.0404)., Conclusions: The geographic relationship between armed conflict and polio incidence provides valuable insights as to how to plan a vaccination campaign in violent contexts, and allows us to anticipate incident polio in the regions of armed conflict. Such information permits vaccination planners to engage interested armed combatants to co-develop strategies to mitigate the effects of violence on polio.

Nigeria has made tremendous strides towards eliminating polio and has been free of wild polio virus (WPV) for more than a year as of August 2015. However, sustained focus towards getting rid of all types of poliovirus by improving population immunity and enhancing disease surveillance will be needed to ensure it sustains the polio-free status. We reviewed the pertinent literature including published and unpublished, official reports and working documents of the Global Polio Eradication Initiative (GPEI) partners as well as other concerned organizations. The literature were selected based on the following criteria: published in English Language, published after year 2000, relevant content and conformance to the theme of the review and these were sorted accordingly. The challenges facing the Polio Eradication Initiative (PEI) in Nigeria were found to fall into 3 broad categories viz failure to vaccinate, failure of the Oral Polio Vaccine (OPV) and epidemiology of the virus. Failure to vaccinate resulted from insecurity, heterogeneous political support, programmatic limitation in implementation of vaccination campaigns, poor performance of vaccination teams in persistently poor performing Local Government areas and sporadic vaccine refusals in Northern Nigeria. Sub optimal effectiveness of OPV in some settings as well as the rare occurrence of VDPVs associated with OPV type 2 in areas of low immunization coverage were also found to be key issues. Some of the innovations which helped to manage the threats to the PEI include a strong government accountability frame work, change from type 2 containing OPV to bi valent OPVs for supplementary immunization activities (SIA), enhancing environmental surveillance in key states (Sokoto, Kano and Borno) along with an overall improvement in SIA quality. There has been an improvement in coverage of routine immunization and vaccination campaigns, which has resulted in Nigeria being removed from the list of endemic countries following an absence of new cases for an entire year as of September 2015. However, the last mile remains to be crossed and there is need to further improve and sustain the momentum to complete the journey toward polio elimination.

This study evaluated the immunogenicity of the human rotavirus (RV) vaccine (RIX4414) when co-administered with routine childhood vaccines in Chinese infants (NCT01171963). Healthy infants aged 6-16 weeks received 2 doses of either RIX4414 or placebo according to a 0, 1-month schedule. Infants received routine diphtheria-tetanus-acellular pertussis (DTPa) and oral poliovirus (OPV) vaccines either separately from or concomitantly with RIX4414/placebo (separate and co-administration cohorts, respectively). Anti-RV IgA seroconversion rates (one month post-dose-2) and seropositivity rates (at one year of age) were measured using ELISA. Immune responses against the DTPa and OPV antigens were measured one month post-DTPa dose-3 in the co-administration cohort. Solicited local and general symptoms were recorded for 8-days post-vaccination (total cohort). The according-to-protocol immunogenicity population included 511 infants in the separate cohort and 275 in the co-administration cohort. One month post-RIX4414 dose-2, anti-RV IgA seroconversion rates were 74.7% (95% confidence interval [CI]: 68.9-79.9) and 64.2% (95% CI: 55.4-72.3) in the separate and co-administration cohorts; seropositivity rates at one year of age were 71.5% (95% CI: 65.5-77.1) and 50.0% (95% CI: 40.9-59.1), respectively. One month post-DTPa dose-3, all infants in the co-administration cohort were seroprotected against diphtheria and tetanus, and seropositive for pertussis toxoid, pertactin and filamentous haemaglutinin. Two months post-OPV dose-3, seroprotection rates against anti-poliovirus types 1, 2 and 3 were >99% in the co-administration cohort. Reactogenicity profiles were similar in both cohorts. RIX4414 was immunogenic and well-tolerated in Chinese infants and did not appear to interfere with the immunogenicity and reactogenicity of co-administered routine childhood vaccines.

World Health Assembly (WHA) in 1988 encouraged the member states to launch Global Polio Eradication Initiative (GPEI) (resolution WHA41.28) against "the Crippler" called poliovirus, through strong routine immunization program and intensified surveillance systems. Since its launch, global incidence of poliomyelitis has been reduced by more than 99 % and the disease squeezed to only three endemic countries (Afghanistan, Pakistan, and Nigeria) out of 125. Today, poliomyelitis is on the verge of eradication, and their etiological agents, the three poliovirus serotypes, are on the brink of extinction from the natural environment. The last case of poliomyelitis due to wild type 2 strain occurred in 1999 in Uttar Pradesh, India whereas the last paralytic case due to wild poliovirus type 3 (WPV3) was seen in November, 2012 in Yobe, Nigeria. Despite this progress, undetected circulation cannot fully rule out the eradication as most of the poliovirus infections are entirely subclinical; hence sophisticated environmental surveillance is needed to ensure the complete eradication of virus. Moreover, the vaccine virus in under-immunized communities can sometimes revert and attain wild type characteristics posing a big challenge to the program.

Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization's Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5' non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.

Introduction: Pakistan accounts for 85.2% of the total polio cases reported worldwide. Healthcare workers (HCWs) are an integral part of immunization campaigns and source of education for the general public. This study aimed to assess the knowledge and attitudes towards polio vaccination among HCWs providing immunisation and education to general public in Quetta and Peshawar divisions of Pakistan., Methods: A cross-sectional survey of 490 HCWs was conducted in two major referral public teaching hospitals of Quetta and Peshawar divisions. During February to April, 2015, a random sample of 490 HCWs was invited to participate in this study. Knowledge and attitudes were assessed by using self-administered, anonymous and pretested questionnaire. Descriptive and logistic regression analyses were used to express the results., Results: A total of 468 participants responded to the questionnaire, giving a response rate of 95.5%. Overall, participants demonstrated good knowledge and positive attitudes towards polio vaccination. The mean knowledge score of HCWs about polio was 13.42 ± 2.39 (based on 18 knowledge questions) while the mean attitude score was 28.75 ± 5.5 (based on 9 attitudes statements). Knowledge gaps were identified about the incubation period of poliovirus (19.5%), management issues (31.9%), use of polio vaccine in mild illnesses (34.7%) and the consequences of the polio virus (36.9%). The majority of participants agreed that all children should be vaccinated for polio (95.1%), while reservations were noted about the need of a booster (38.9%), and sterility issues associated with polio vaccines (43.6%). Internet (n = 167, 37%) and Posters (n = 158, 35%) were the main sources used by HCWs to educate themselves about polio., Conclusion: Participants in this study had good knowledge and positive attitudes towards polio vaccination. Although the data are indicative of gaps in the knowledge of HCWs, the findings may not be generalized to other hospitals in Pakistan.

To analyze the genetic characteristics of a polio-I highly variant vaccine recombinant virus in Shandong Province (China) in 2011 and to identify isolates from healthy contacts, two stool specimens from one patient with acute flaccid paralysis (AFP) and 40 stool specimens from his contacts were collected for virus isolation. The complete genome of poliovirus and VP1 coding region of the non-polio enterovirus were sequenced. Homologous comparison and phylogenetic analyses based on VP1 sequences were undertaken among coxsackievirus (CV) B1, CV-B3 isolates, and those in GenBank. One poliovirus (P1/11186), CV-A4 and CV-A8 were isolated from the AFP patient; one CV-A2, Echovirus 3 (E-3), E-12 and E-14, ten CV-B1, and five CV-B3 strains were isolated from his contacts. These results led us to believe that there may be a human enterovirus epidemic in this area, and that surveillance must be enhanced. P1/11186 was a type-1 vaccine-related poliovirus; it combined with type-2 and type-3 polioviruses in 2A and 3A regions, respectively. There were 25 nucleotide mutations with 9 amino-acid alterations in the entire genome. There were 8 nucleotide mutations with 5 amino-acid alterations in the VP1 region compared with the corresponding Sabin strains. Homology analyses suggested that the ten CV-B1 isolates had 97.0%-100% nucleotide and 98.9%-100% amino-acid identities with each other, as well as 92.6%-100% nucleotide and 99.2%-100% amino-acid identities among the five CV-B3 isolates. Phylogenetic analyses on the complete sequences of VP1 among CV-B1 and CV-B3 isolates showed that Shandong strains, together with strains from other provinces in China, had a close relationship and belonged to the same group.

There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.