Poliovirus Research Articles

Oral booster vaccine antigen-Expression of full-length native SARS-CoV-2 spike protein in lettuce chloroplasts.

Oral booster vaccine antigen-Expression of full-length native SARS-CoV-2 spike protein in lettuce chloroplasts.

REASONS OF REFUSING POLIO VACCINATION AMONG PARENTS OF UNDER-5 YEARS CHILDREN IN DISTRICT MULTAN, PAKISTAN

Background and Objective: Polio is still endemic in Pakistan and Afghanistan. In Pakistan, transmission of polio virus is high due to poor political environment and internal security threats especially in war against terrorism in Swat and FATA. Meanwhile, some groups tried to create misconception about polio vaccine. The objective of the study was to describe the reasons underpinning the refusals to polio vaccine in District Multan.
 Methods:- This descriptive, cross sectional study was conducted in a District Multan. A closed ended pre- tested questionnaire in Urdu language was used to collect data from 34 parents of under five year children, who refused polio vaccaniation during polio compaign.
 Results:- Out of 34 polio vaccine refusal parents, 15 did not respond or either locked the doors as researcher tried to interview them. About 29% refusing parents mentioned religious reasons, about 42% have apprehensions on polio vaccine contents. One third reported that it was a western world conspricy against mullims. 45% states that government vaccine supply is of poor quality, as the main factor for refusal.
 Conclusion: Majority of refusing parents were uncomfortable in responding to the survey or either they were never counseled for Polio and now they are habitual refusals or may be perception about polio vaccine is negative. In District Multan, religious reasons and misconception that vaccine causes sterility in male children were main reasons of polio vaccine refusal. Efforts will be required in changing the perception of parents.

Establishment of measles virus receptor-expressing Vero cells lacking functional poliovirus receptors.

Global efforts are underway to eliminate measles and rubella, and active viral surveillance is the key to achieving this goal. In addition, the World Health Organization announced guidelines for handling materials potentially infectious for poliovirus (PV) to minimize the risk of PV reintroduction and to achieve PV eradication. To support global efforts, we established new PV-non-susceptible cell lines that are useful for the isolation of measles virus (MeV) and rubella virus (RuV) (Vero ΔPVR1/2 hSLAM+). In the cell lines, MeV and RuV replicated efficiently, with no concern regarding PV replication.

Seroprevalence of poliovirus antibodies in Nigeria: refining strategies to sustain the eradication effort.

in 2016, a switch from trivalent oral poliovirus vaccine (OPV) (containing serotypes 1,2,3) to bivalent OPV (types 1,3) was implemented globally. We assessed the seroprevalence of poliovirus antibody levels in selected Nigerian states, before and after the switch, documented poliovirus type2 outbreak responses conducted and ascertained factors associated with immunity gaps based on seroprevalence rates. we conducted a secondary analysis of stored serum samples from the 2018 Nigeria National HIV/AIDS Indicator and Impact Survey. Serum from 1,185 children aged 0-119 months residing in one southern and four northern states were tested for serotype-specific PV neutralizing antibodies; seropositivity was a reciprocal titer ≥8. We conducted regression analysis to determine sociodemographic risk factors associated with low seroprevalence using SAS 9.4. children aged 24-119 months (pre-switch cohort) had seroprevalence against PV1, PV2, and PV3, of 97.3% (95% CI:96.4-98.2), 93.8% (95% CI:92.2-95.5), and 91.3% (95% CI:89.2-93.4), while children aged <24 months (post-switch) had seroprevalence of 86.0% (95% CI:81.2-90.8), 55.6% (95% CI: 47.7-63.4), and 77.2% (95% CI:71.0-83.4) respectively. Regression analysis showed age <24 months was associated with lower seroprevalence against all PV serotypes, (p<0.0001); females had lower seroprevalence against PV1 (p=0.0184) and PV2 (p=0.0354); northern states lower seroprevalence against PV1 (p=0.0039), while well-water source lower seroprevalence against PV3 (p=0.0288). this study showed high seroprevalence rates against PV 1, 2, and 3 in pre-switch children (aged 24-119 months). However, post-switch children (<24 months) had low immunity against PV2 despite outbreak responses. Strategies to increase routine immunization coverage and high-quality polio campaigns can increase immunity against polio virus.

The role of transformational leadership in polio eradication in pakistan

Polio is still endemic, along with the COVID-19 pandemic, which presents severe threats to public health. Polio is a serious disease caused by the polio virus and can lead to disability and paralysis in certain parts of the body. The need for strong and visionary leadership in addressing the challenges associated with polio and achieving effective eradication is being examined, particularly the role of transformational leadership in Pakistan. The goal is to demonstrate how transformational leadership can mobilize resources, engage communities, and lead coordinated efforts toward the objective of making Pakistan polio-free, through the study of the impact of this leadership style. Transformational leadership focuses on building trustworthy relationships and instigating change based on core values. It aims to inspire and motivate subordinates and followers, transforming their beliefs, attitudes, and behaviors to accomplish both planning and goals. Only two countries are left in the world where polio cases are reported: Pakistan and Afghanistan. Leadership incompetency is the primary reason for the persistence of the polio virus in these nations. Transformative nursing leadership plays a crucial role in effectively eradicating polio in Pakistan. The challenges include limited resources, cultural and societal barriers, safety and security concerns, and vaccine hesitancy among the population. Transformational leaders in both countries have the potential to motivate stakeholders to unite in the fight against polio, ultimately eradicating this menace from our nations collectively.

Field Monitoring of the Implementation of Polio Supplementary Immunization Activities Following Circulating Vaccine-Derived Polio Virus Type 2 (CVDPV2) Outbreak in Aceh, Indonesia

Field Monitoring of the Implementation of Polio Supplementary Immunization Activities Following Circulating Vaccine-Derived Polio Virus Type 2 (CVDPV2) Outbreak in Aceh, Indonesia

Five decades of infectious diseases outbreaks in the African region (1970–2018) a geographic snapshot

This paper is being written at a time when the recent pandemic, namely COVID-19, has shaken the entire world in a manner that has never been seen in modern history. The ecology, socio-economy and weak health systems make Africa an area favorable to the occurrence of various diseases and disease outbreaks. This paper explores forty-eight (48) years of disease outbreaks in the WHO African region of the World Health Organization (WHO). Twenty-five (25) Integrated Disease Surveillance and Response priority diseases were selected, and their outbreaks were described and analyzed. Using inferential spatial statistics, spatial clusters at the health district level, specifically hot spots of those outbreaks, were produced and analyzed. The Population at risk of those hot spots was estimated. Results show a consistent report of outbreaks during the selected period, with 52 outbreaks on average per year. Poliomyelitis, cholera, yellow fever, meningococcal disease and measles were the most reported outbreaks. Democratic Republic of the Congo (DRC) and Nigeria were the countries reporting the highest number of outbreaks (5 on average per year), with high number of people living in hot spots districts (85M). Despite efforts to limit their number, some disease outbreaks, such as cholera, malaria, and measles, continue to have a burden in terms of morbidity and mortality. In contrast, others, such as poliomyelitis, yellow fever and diarrhoeal disease, have shown a declining trend, and wild polio virus transmission has been eliminated in the region. Results suggest that concerted public health action may help reduce outbreaks in the region. Results can be used to inform preparedness and prevention activities. Priority public health actions should target DRC and Nigeria and identified hot spots and areas with existing risk factors within other countries.

Identification of the Intrinsic Motions and Related Key Residues Responsible for the Twofold Channel Opening of Poliovirus Capsid by Using an Elastic Network Model Combined with an Internal Coordinate.

Poliovirus (PV) is an infectious virus that causes poliomyelitis, which seriously threatens the health of children. The release of viral RNA is a key step of PV in host cell infection, and multiple lines of evidence have demonstrated that RNA release is initiated by the opening of the twofold channels of the PV capsid. However, the mechanism that controls the twofold channel opening is still not well understood. In addition, the channel opening motion of the recombinant PV capsid leads to the destruction of predominant neutralizing epitopes and thus hinders the capsid as a vaccine immunogen. Therefore, it is important to identify the intrinsic motions and the related key residues controlling the twofold channel opening for understanding the virus infection mechanism and developing capsid-based vaccines. In the present work, the width of the channel was selected as an internal coordinate directly related to the channel opening, and then the elastic network model (ENM) combined with the group theory were employed to extract the intrinsic motion modes that mostly contribute to the opening of the twofold channels. Our results show that the channel opening predominately induced by the breathing motion and the overall rotation of each protomer in the capsid. Then, an internal coordinate-based perturbation method was used to identify the key residues regulating the twofold channel opening of PV. The calculation results showed that the predicted key residues are mainly located at the twofold axes, the bottom of the canyons and the quasi threefold axes. Our study is helpful for better understanding the twofold channel opening mechanism and provides a potential target for preventing the opening of the channels, which is of great significance for PV vaccine design. The source code of this study is available at https://github.com/SJGLAB/CapsidKeyRes.git.

Protease-Independent Production of Poliovirus Virus-like Particles in Pichia pastoris: Implications for Efficient Vaccine Development and Insights into Capsid Assembly.

The production of enterovirus virus-like particles (VLPs) that lack the viral genome have great potential as vaccines for a number of diseases, such as poliomyelitis and hand, foot, and mouth disease. These VLPs can mimic empty capsids, which are antigenically indistinguishable from mature virions, produced naturally during viral infection. Both in infection and in vitro, capsids and VLPs are generated by the cleavage of the P1 precursor protein by a viral protease. Here, using a stabilized poliovirus 1 (PV-1) P1 sequence as an exemplar, we show the production of PV-1 VLPs in Pichia pastoris in the absence of the potentially cytotoxic protease, 3CD, instead using the porcine teschovirus 2A (P2A) peptide sequence to terminate translation between individual capsid proteins. We compare this to protease-dependent production of PV-1 VLPs. Analysis of all permutations of the order of the capsid protein sequences revealed that only VP3 could be tagged with P2A and maintain native antigenicity. Transmission electron microscopy of these VLPs reveals the classic picornaviral icosahedral structure. Furthermore, these particles were thermostable above 37°C, demonstrating their potential as next generation vaccine candidates for PV. Finally, we believe the demonstration that native antigenic VLPs can be produced using protease-independent methods opens the possibility for future enteroviral vaccines to take advantage of recent vaccine technological advances, such as adenovirus-vectored vaccines and mRNA vaccines, circumventing the potential problems of cytotoxicity associated with 3CD, allowing for the production of immunogenic enterovirus VLPs in vivo. IMPORTANCE The widespread use of vaccines has dramatically reduced global incidence of poliovirus infections over a period of several decades and now the wild-type virus is only endemic in Pakistan and Afghanistan. However, current vaccines require the culture of large quantities of replication-competent virus for their manufacture, thus presenting a potential risk of reintroduction into the environment. It is now widely accepted that vaccination will need to be extended posteradication into the foreseeable future to prevent the potentially catastrophic reintroduction of poliovirus into an immunologically naive population. It is, therefore, imperative that novel vaccines are developed which are not dependent on the growth of live virus for their manufacture. We have expressed stabilized virus-like particles in yeast, from constructs that do not require coexpression of the protease. This is an important step in the development of environmentally safe and commercially viable vaccines against polio, which also provides some intriguing insights into the viral assembly process.

Essential Domains of Oxysterol-Binding Protein Required for Poliovirus Replication.

Oxysterol-binding protein (OSBP) is a host factor required for enterovirus (EV) replication. OSBP locates at membrane contact site and acts as a lipid exchanger of cholesterol and phosphatidylinositol 4-phosphate (PI4P) between cellular organelles; however, the essential domains required for the viral replication remain unknown. In this study, we define essential domains of OSBP for poliovirus (PV) replication by a functional dominance assay with a series of deletion variants of OSBP. We show that the pleckstrin homology domain (PHD) and the ligand-binding domain, but not the N-terminal intrinsically disordered domain, coiled-coil region, or the FFAT motif, are essential for PV replication. The PHD serves as the primary determinant of OSBP targeting to the replication organelle in the infected cells. These results suggest that not all the domains that support important biological functions of OSBP are essential for the viral replication.

Advancements in assay &amp; analytic development in the vaccines field

Charlotte Barker, Editor, BioInsights, speaks to Jessica White, Vaccine Formulations Team, PATH, about her career in immunology and infectious disease, and her recent work on in vitro inhibition ELISA assaysJessica White is a virologist who has been working at PATH for the past 10 years on the Vaccine and Pharmaceutical formulation technologies and the Chemistry and Manufacturing Controls teams. She has a PhD in Comparative Pathology from University of California, Davis and completed two postdoctoral positions at University of Washington as a research fellow in Infectious Diseases and Immunology and one at PATH in vaccine formulation. Jessica supports the development of vaccine candidates for Shigella, E. coli, Rotavirus, Measles and Rubella, Novel Oral Polio Virus, Non-Salmonella Typhoid, and SARS CoV-2. To improve global access to these critical immunizations, her team specializes in producing novel thermostable and needle-free vaccine formats, such as fast dissolving tablets. Currently, Jessica is leading the work to produce and characterize monoclonal antibodies specific against the SARS CoV-2 variants for use by vaccine manufacturers and researchers.

A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV. We report cryo-EM structures of GSH bound to PV serotype 3 VLPs showing that it can enhance particle stability. GSH binds the positively charged pocket at the interprotomer interface shown recently to bind GSH in enterovirus F3 and putative antiviral benzene sulphonamide compounds in other enteroviruses. We show, using high-resolution cryo-EM, the binding of a benzene sulphonamide compound with a PV serotype 2 VLP, consistent with antiviral activity through over-stabilizing the interprotomer pocket, preventing the capsid rearrangements necessary for viral infection. Collectively, these results suggest GSH or an analogous tight-binding antiviral offers the potential for stabilizing VLP vaccines.

A phase I, open label, clinical study to assess the safety and immunogenicity of indigenously developed liquid (DTwP-HepB-IPV-Hib) hexavalent combination vaccine in healthy toddlers aged 16–24 months

ABSTRACT This first in human study was designed as an open label clinical trial to assess the safety and immunogenicity of SIIPL DTwP-HepB-IPV-Hib (Hexavalent) combination vaccine in healthy toddlers, aged 16–24 months. A total of 24 healthy toddlers were administered a 0.5 ml single dose of SIIPL DTwP-HepB-IPV-Hib vaccine intramuscularly, and followed for 28 days for safety outcomes viz. immediate, solicited, unsolicited and serious adverse events. Blood samples were collected immediately prior to and 28 days after vaccination to assess the immunogenicity. Twenty four completed the study in compliance with the study protocol. None of the participants experienced any immediate or any serious adverse event. In terms of the frequency and intensity, the adverse events were comparable to DTwP-based combination vaccines. The vaccine elicited a strong booster response as demonstrated by a large increase in antibodies against all vaccine antigens. One month post booster vaccination seroprotection for diphtheria, tetanus, Hepatitis B, Haemophilus influenzae type b and polio virus type 1 and 3 was 100%. The percentage sero-response for pertussis was 75%. Four-fold increase in antibody concentration for pertussis was achieved in 87.5% subjects. Indigenously developed DTwP-HepB-IPV-Hib vaccine by Serum Institute of India Pvt. Ltd. was found to be safe, well tolerated and showed a robust immune response in toddlers. It was concluded that this vaccine should be assessed in the next phases of clinical development in the target population. Clinical Trial Registration – CTRI/2018/10/015875.

Tracking down the recent surge of polio virus in endemic and outbreak countries.

Continuous and progressive efforts are being made globally to eradicate the incidence of poliovirus. The detrimental nature of polio calls for action of global vaccination. Owing to large-scale vaccination efforts, many countries have been declared polio-free and people are fully vaccinated against poliovirus. However, concern still remains as new cases are being identified in countries declared polio-free. This scenario is particularly noticed due to the comprised healthcare system in the past 3 years of the Corona pandemic. Conditions for lower-middle-income countries are more problematic, where there are meager healthcare resources and the burden on the healthcare system is higher. Studies indicate some cases of non-paralytic species of polio including cVDPV1, cVDPV2, and cVDPV3 in the group of outbreak countries. However, the major problem is associated with wild-type poliovirus, that is,WPV1 which leads to paralytic disease and is still present in endemic countries, such as Afghanistan and Pakistan. The incidence rate of wild polio cases has significantly decreased in comparison to the past years but the problem needs to be dealt with at the grass-roots level. In this article, the most recent data havebeen collected pertaining to the incidence of multivariant species of poliovirus, with a special focus on endemic and outbreak countries. A short overview of challenges to vaccination and a recommendatory overview has also been included for dealing with polio surges.

A Short 5'triphosphate RNA nCoV-L Induces a Broad-Spectrum Antiviral Response by Activating RIG-I.

Small molecular nucleic acid drugs produce antiviral effects by activating pattern recognition receptors (PRRs). In this study, a small molecular nucleotide containing 5'triphosphoric acid (5'PPP) and possessing a double-stranded structure was designed and named nCoV-L. nCoV-L was found to specifically activate RIG-I, induce interferon responses, and inhibit duplication of four RNA viruses (Human enterovirus 71, Human poliovirus 1, Human coxsackievirus B5 and Influenza A virus) in cells. In vivo, nCoV-L quickly induced interferon responses and protected BALB/c suckling mice from a lethal dose of the enterovirus 71. Additionally, prophylactic administration of nCoV-L was found to reduce mouse death and relieve morbidity symptoms in a K18-hACE2 mouse lethal model of SARS-CoV-2. In summary, these findings indicate that nCoV-L activates RIG-I and quickly induces effective antiviral signals. Thus, it has potential as a broad-spectrum antiviral drug.

In vitro antiviral activities of fruit extract from Lycium barbarum and methylxanthines extracted from Pu-erh and Bancha tea leaves.

Based on traditional medicine, many countries use various plant products (fruits, leaves and other plant parts) as food supplements or in the form of tea. The use of these plant sources has been established through the years of use and the proven benefits of their ingredients to improve human health.

Human poliovirus receptor contributes to biliary atresia pathogenesis by exacerbating natural-killer-cell-mediated bile duct injury.

Natural killer (NK) cells play an important role in biliary atresia (BA) pathogenesis; human poliovirus receptor (PVR) is an important NK-cell modulator. Here, we explored the role of PVR in BA pathogenesis. Poliovirus receptor expression and NK cell-associated genes were detected in human BA samples and a rotavirus-induced BA mouse model using quantitative PCR and immunofluorescence staining. Chemically modified small interfering RNA silenced PVR expression in the BA model, and its effects on the population and function of intrahepatic NK cells were investigated using flow cytometry (FCM). The effects of PVR overexpression and knockdown on proliferation, apoptosis and NK-cell-mediated lysis of cultured human cholangiocytes were analysed using FCM and cell viability assays. Serum PVR, high-mobility group box 1 (HMGB1), and interleukin-1beta (IL-1beta) levels were measured in a cohort of 50 patients using ELISA. Poliovirus receptor expression was upregulated in the biliary epithelium of BA patients and BA model and was positively correlated with the population and activation of intrahepatic NK cells. Silencing of PVR expression impaired the cytotoxicity of NK cells, reduced inflammation and protected mice from rotavirus-induced BA. Activation of the TLR3-IRF3 signalling pathway induced PVR expression in cultured cholangiocytes. PVR overexpression promoted proliferation and inhibited the apoptosis of cholangiocytes but exacerbated NK cell-mediated cholangiocyte lysis. Serum PVR levels were elevated in BA patients and were positively correlated with HMGB1 and IL-1beta levels. Poliovirus receptor contributes to BA pathogenesis by regulating NK cell-mediated bile duct injury; PVR has the value as a biomarker of BA.

Antiviral Activity of Ficus rubiginosa Leaf Extracts against HSV-1, HCoV-229E and PV-1.

Ficus rubiginosa plant extract showed antimicrobial activity, but no evidence concerning its antiviral properties was reported. The antiviral activity of the methanolic extract (MeOH) and its n-hexane (H) and ethyl acetate (EA) fractions against Herpes simplex virus-1 (HSV-1), Human coronavirus (HCoV) -229E, and Poliovirus-1 (PV-1) was investigated in the different phases of viral infection in the VERO CCL-81 cell line. To confirm the antiviral efficacy, a qPCR was conducted. The recorded cytotoxic concentration 50% was 513.1, 298.6, and 56.45 µg/mL for MeOH, H, and EA, respectively, assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay after 72 h of treatment. The Ficus rubiginosa leaf extract inhibited the replication of HSV-1 in the early stages of infection, showing a complete inhibition up to 0.62, 0.31, and 1.25 µg/mL. Against HCoV-229E, a total inhibition up to 1.25 µg/mL for MeOH and H as well as 5 µg/mL for EA was observed. Otherwise, no activity was recorded against PV-1. The leaf extract could act directly on the viral envelope, destructuring the lipid membrane and/or directly blocking the enriched proteins on the viral surface. The verified gene inhibition suggested that the treatments with M, H, and EA impaired HSV-1 and HCoV-229E replication, with a greater antiviral efficiency against HSV-1 compared to HCoV-229E, possibly due to a greater affinity of Ficus rubiginosa towards membrane glycoproteins and/or the different lipid envelopes.

The fight against poliomyelitis through the history: past, present and hopes for the future. Albert Sabin's missing Nobel and his “gift to all the world's children”

Polio, or poliomyelitis, is a disabling and life-threatening disease caused by three poliovirus (PV) serotypes. The virus spreads from person to person and can infect a person’s spinal cord, causing paralysis. In 1988, when the WHO registered 350,000 cases of poliomyelitis in the world and 70,000 which occurred in Africa alone, global poliomyelitis eradication was proposed by the World Health Organization to its member States. On 25 August 2020, while the world was waging war against the Coronavirus pandemic, a historic milestone was reached: Africa was officially declared polio-free.It is an important result obtained thanks to an intensive large-scale vaccination campaign.The road was far from smooth, nevertheless, according to the WHO, a great effort needs to be made in order to facilitate access to vaccination and to promote its implementation in those countries where coverage is low and vaccine hesitancy is high because the risk of the spread of poliomyelitis is still relevant. Eradication of the virus in Africa provides us with an excellent opportunity to commemorate the many scientists who contributed to achieving this epoch-making goal: first of all, Jonas Salk, who developed a killed-virus vaccine in 1952, and, especially, Albert Sabin, who in 1961 launched programs of mass immunisation with his oral vaccine against poliomyelitis.

Production and Characterisation of Stabilised PV-3 Virus-like Particles Using Pichia pastoris.

Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using Pichia pastoris, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using Pichia pastoris. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV