Establishment of the Daucus carota SMC-1 Cell Suspension Line for Poliovirus Vaccine Development.

The development of virus-free, oral vaccines against poliovirus capable of inducing mucosal protective immunity is needed to safely combat this pathogen. In the present study, a carrot cell line expressing the poliovirus VP2 antigen was established at the level of callus and cell suspensions, exploring the effects of culture media (MS and B5), supplementation with urea, phytoregulators (2,4-D : KIN), and light conditions (continuous light, photoperiod, and total darkness). The best callus growth was obtained on B5 medium supplemented with 2 mg/L of 2,4-D + 2 mg/L kinetin and 0.0136 g/L of urea and in continuous light conditions. Suspension cultures of the SMC-1 line in 250 mL Erlenmeyer flasks had a maximum growth of 16.07 ± 0.03 g/L DW on day 12 with a growth rate of µ=0.3/d and a doubling time of 2.3 days. In a 2 L airlift bioreactor, the biomass yield achieved was 25.6 ± 0.05 g/L DW at day 10 with a growth rate of µ= 0.58/d and doubling time of 1.38 d. Cell growth was 1.5 times higher in bioreactors than in shake flasks, highlighting that both systems resulted in the accumulation of VP2 throughout the time in culture. The maximum VP2 yield in flasks was 387.8 µg/g DW at day 21, while in the reactor it was 550.2 µg/g DW at day 18. In conclusion, bioreactor-based production of the VP2 protein by the SMC-1 suspension cell line offers a higher productivity when compared to flask cultures, offering a key perspective to produce low-cost vaccines against poliomyelitis.

Polio outbreak response, Yemen.

Problem: A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains. Approach: In response to polio outbreaks, the Yemeni health ministry and partners initiated multiple vaccination campaigns to deliver vaccines to children. We also implemented several measures to enhance communication, education, health promotion and hygiene, especially in camps for internally displaced people. Local setting: In 2009, Yemen achieved polio-free status and maintained it until 2019. However, the ongoing political conflict since 2015, coupled with challenges in delivering the polio vaccine to conflict-affected areas, resulted in two polio outbreaks: 35 cases caused by vaccine-derived poliovirus strain 1 between 2019 and 2021, and 230 cases due to vaccine-derived poliovirus strain 2 between November 2021 and December 2022. Relevant changes: In response to the first outbreak, by the end of 2020, we vaccinated 7.2 million children through nationwide vaccination campaigns, except in Sa'ada governorate due to a ban by the authorities. By the end of 2021, 3 800 313 children younger than 5 years had received polio vaccines. For the second outbreak, by the end of 2022, 4 463 389 vaccines had been given to children younger than 10 years, and 1 217 423 to those younger than 5 years. Lessons learnt: Vaccination campaigns in conflict-affected areas with low vaccine coverage remain crucial in eradicating polio. Efforts are needed to reach vulnerable groups such as displaced populations. Advocacy, communication and social mobilization actions help ensure broader public inclusion and participation in vaccination efforts to prevent polio outbreaks.

Oral polio vaccine stockpile modeling: insights from recent experience.

BACKGROUND: Achieving polio eradication requires ensuring the delivery of sufficient supplies of the right vaccines to the right places at the right times. Despite large global markets, decades of use, and large quantity purchases of polio vaccines by national immunization programs and the Global Polio Eradication Initiative (GPEI), forecasting demand for the oral poliovirus vaccine (OPV) stockpile remains challenging. RESEARCH DESIGN AND METHODS: We review OPV stockpile experience compared to pre-2016 expectations, actual demand, and changes in GPEI policies related to the procurement and use of type 2 OPV vaccines. We use available population and immunization schedule data to explore polio vaccine market segmentation, and its role in polio vaccine demand forecasting. RESULTS: We find that substantial challenges remain in forecasting polio vaccine needs, mainly due to (1) deviations in implementation of plans that formed the basis for earlier forecasts, (2) lack of alignment of tactics/objectives among GPEI partners and other key stakeholders, (3) financing, and (4) uncertainty about development and licensure timelines for new polio vaccines and their field performance characteristics. CONCLUSIONS: Mismatches between supply and demand over time have led to negative consequences associated with both oversupply and undersupply, as well as excess costs and potentially preventable cases.

Prevalence of poliovirus neutralizing antibodies in Italian population: A systematic review and meta-analysis.

INTRODUCTION: The introduction of anti-poliomyelitis vaccines has driven progress toward the global eradication of wild polioviruses, a millennium goal of the World Health Organization. With the vaccination campaigns carried out since 1964, in 2002 Italy was certified polio-free, considering that no cases had been recorded since 1983. Nevertheless, it is crucial to guarantee high level of immunization coverage also in low-endemicity countries, considering that sporadic polio cases can be recorded. To evaluate the presence of susceptible subjects in the population, seroepidemiological studies are key actions. METHODS: We conducted a systematic review of the relevant literature to evaluate the prevalence of anti-PV neutralizing antibodies in Italian population. Seven studies, selected among scientific articles available in MEDLINE/PubMed, ISI Web of Knowledge and Scopus and published from January 1, 2012, to November 15, 2022, were included. RESULTS: The pooled prevalence of subjects without PV1 neutralizing antibodies was 6.4% (95%CI = 0.5-16.9), for PV2 it was 5.3% (95%CI = 0.4-14.2), and for PV3 it was 13.0% (95%CI = 4.0-25.7; I2 = 98.5%). Levels of neutralizing antibodies appears to decrease with increasing age; this decline is a proxy for the real risk factor, which is the time since the last vaccine dose. CONCLUSIONS: Public health institutions must be aware of the risk of reintroduction of wild PV in polio-free countries and therefore they must keep high level of immunization in population and reinforce the active surveillance systems.

Polio eradication: Addressing the hurdles on the last mile.

1988, the World Health Assembly committed to eradicate poliomyelitis, a viral disease that can cause permanent paralysis. Today, only type 1 of the three wild poliovirus types remains circulating in limited geographic areas following widespread use of different poliovirus vaccines. While we are close to zero new cases of wild polio, it is a fragile situation, and there are many remaining and new hurdles to overcome. Here, experts discuss how to address them.

Is it time to switch to a formulation other than the live attenuated poliovirus vaccine to prevent poliomyelitis?

The polioviruses (PVs) are mainly transmitted by direct contact with an infected person through the fecal-oral route and respiratory secretions (or more rarely via contaminated water or food) and have a primary tropism for the gut. After their replication in the gut, in rare cases (far less than 1% of the infected individuals), PVs can spread to the central nervous system leading to flaccid paralysis, which can result in respiratory paralysis and death. By the middle of the 20th century, every year the wild polioviruses (WPVs) are supposed to have killed or paralyzed over half a million people. The introduction of the oral poliovirus vaccines (OPVs) through mass vaccination campaigns (combined with better application of hygiene measures), was a success story which enabled the World Health Organization (WHO) to set the global eradication of poliomyelitis as an objective. However this strategy of viral eradication has its limits as the majority of poliomyelitis cases today arise in individuals infected with circulating vaccine-derived polioviruses (cVDPVs) which regain pathogenicity following reversion or recombination. In recent years (between January 2018 and May 2023), the WHO recorded 8.8 times more cases of polio which were linked to the attenuated OPV vaccines (3,442 polio cases after reversion or recombination events) than cases linked to a WPV (390 cases). Recent knowledge of the evolution of RNA viruses and the exchange of genetic material among biological entities of the intestinal microbiota, call for a reassessment of the polio eradication vaccine strategies.

Descriptive epidemiology of poliomyelitis cases due to wild poliovirus type 1 and wild poliovirus type 3 in Nigeria, 2000-2020.

Introduction: in August 2020, the World Health Organization African Region was certified free of wild poliovirus (WPV) when Nigeria became the last African country to interrupt wild poliovirus transmission. The National Polio Emergency Operations Center instituted in 2012 to coordinate and manage Nigerian polio eradication efforts reviewed the epidemiology of WPV cases during 2000-2020 to document lessons learned. Methods: we analyzed reported WPV cases by serotype based on age, oral poliovirus vaccine immunization history, month and year of reported cases, and annual geographic distribution based on incidence rates at the Local Government Area level. The observed trends of cases were related to major events and the poliovirus vaccines used during mass vaccination campaigns within the analysis period. Results: a total of 3,579 WPV type 1 and 1,548 WPV type 3 laboratory-confirmed cases were reported with onset during 2000-2020. The highest WPV incidence rates per 100,000 population in Local Government Areas were 19.4, 12.0, and 11.3, all in 2006. Wild poliovirus cases were reported each year during 2000-2014; the endemic transmission went undetected throughout 2015 until the last cases in 2016. Ten events/milestones were highlighted, including insurgency in the northeast which led to a setback in 2016 with four cases from children previously trapped in security-compromised areas. Conclusion: Nigeria interrupted WPV transmission despite the challenges faced because of the emergency management approach, implementation of mass vaccination campaigns, the commitment of the government agencies, support from global polio partners, and special strategies deployed to conduct vaccination and surveillance in the security-compromised areas.

Enterovirus detection in different regions of Madagascar reveals a higher abundance of enteroviruses of species C in areas where several outbreaks of vaccine-derived polioviruses occurred.

BACKGROUND: Poliomyelitis outbreaks due to pathogenic vaccine-derived polioviruses (VDPVs) are threatening and complicating the global polio eradication initiative. Most of these VDPVs are genetic recombinants with non-polio enteroviruses (NPEVs) of species C. Little is known about factors favoring this genetic macroevolution process. Since 2001, Madagascar has experienced several outbreaks of poliomyelitis due to VDPVs, and most of VDPVs were isolated in the south of the island. The current study explored some of the viral factors that can promote and explain the emergence of recombinant VDPVs in Madagascar. METHODS: Between May to August 2011, we collected stools from healthy children living in two southern and two northern regions of Madagascar. Virus isolation was done in RD, HEp-2c, and L20B cell lines, and enteroviruses were detected using a wide-spectrum 5'-untranslated region RT-PCR assay. NPEVs were then sequenced for the VP1 gene used for viral genotyping. RESULTS: Overall, we collected 1309 stools, of which 351 NPEVs (26.8%) were identified. Sequencing revealed 33 types of viruses belonging to three different species: Enterovirus A (8.5%), Enterovirus B (EV-B, 40.2%), and Enterovirus C (EV-C, 51.3%). EV-C species included coxsackievirus A13, A17, and A20 previously described as putative recombination partners for poliovirus vaccine strains. Interestingly, the isolation rate was higher among stools originating from the South (30.3% vs. 23.6%, p-value = 0.009). EV-C were predominant in southern sites (65.7%) while EV-B predominated in northern sites (54.9%). The factors that explain the relative abundance of EV-C in the South are still unknown. CONCLUSIONS: Whatever its causes, the relative abundance of EV-C in the South of Madagascar may have promoted the infections of children by EV-C, including the PV vaccine strains, and have favored the recombination events between PVs and NPEVs in co-infected children, thus leading to the recurrent emergence of recombinant VDPVs in this region of Madagascar.

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.

Vacina Mais enfatiza importância da vacinação contra poliomielite no Brasil em novas peças de campanha

A Campanha Vacina Mais disponibilizou um novo pacote de peças de comunicação que abordam a importância da vacinação contra a poliomielite, também conhecida como paralisia infantil.

Understanding the reasons for refusal of polio vaccine by families in Quetta Block, Pakistan.

Background: Global polio eradication is a goal yet to be achieved in countries like Pakistan. In recent years, the Polio Eradication Initiative has been making steady progress with good campaign coverage and low numbers of polio cases. However, in 2019 Pakistan reported 146 cases compared to 12 in 2018. A major factor cited for this regression was a surge in vaccine refusals by parents and caretakers. Aims: To assess the reasons for the refusal of polio vaccination in Quetta Block, Balochistan. Methods: The study was conducted using data acquired from 2 polio vaccination campaigns over 3 months in 2019. The data were collected in Quetta Block, a highly endemic zone having continuous transmission of the polio virus over several years. The data were analysed using the statistical software, SPSS, version 20. We used descriptive statistics to demonstrate the characteristics of the study population. Categorical variables were measured as frequencies and percentages. Results: Refusal rates were almost 8.6% for the polio campaign of April and 8.1% for June 2019. Misconceptions about vaccines made up 56.4% of reasons for refusals, followed by religion 16%. Conclusion: Misconceptions about the vaccine are the main driving force behind vaccine refusals in the study setting. Efficient strategies are required to address misconceptions in this red zone of poliovirus transmission in Balochistan.

Pólio: baixa cobertura vacinal e o risco iminente de novas infecções / Polio: low vaccination coverage and the imminent risk of new infections

A poliomielite, comumente chamada de pólio ou paralisia infantil, é uma doença viral altamente infecciosa que afeta principalmente crianças menores de 5 anos de idade. O vírus é transmitido de pessoa para pessoa, disseminado principalmente pela via fecal-oral ou, menos frequentemente, por fômites (água ou alimentos contaminados); sendo que o agente etiológico pode se espalhar rapidamente em áreas cujos sistemas de higiene e saneamento são precários. Também pode haver transmissão por meio de gotículas de secreções da garganta durante a fala, tosse ou espirro ( WHO, 20 22 a ; SBIm, 2022)

Polio, commonly called polio or infantile paralysis, is a highly infectious viral disease that primarily affects children under 5 years of age. The virus is transmitted from person to person, spread mainly by the fecal-oral route or, less frequently, by fomites (contaminated water or food); being that the agent etiologic disease can spread rapidly in areas where hygiene and sanitation systems are precarious. There may also be transmission through droplets of secretions from the throat during speech, coughing or sneezing (WHO, 20 22 a ; SBIm, 2022)

Group influence on attitudes towards polio vaccination in Pakistan: Role of group identification and perceived group support for polio vaccines.

Objectives: To study the moderating role of perceived group normative support on the effect of group identification on scepticism and advocacy domains of attitude towards polio vaccination. METHODS: The cross-sectional analytical study was conducted at the National Institute of Psychology, Quaid-i-Azam University, Islamabad, Pakistan, in June 2020, and comprised adult residents of Pakistan who were approached through online platform Psytoolkit. Data was collected by means of Attitude towards Polio Vaccination Scale, Group Identification Scale, and a measure of Perceived Group Normative Support for Polio Vaccination. Data was analysed using SPSS 21. RESULTS: Of the 310 participants, 69(22.3%) were men and 240(77.4%) were women. The overall mean age was 25.62±8.47 years (range: 18-72 years). Further, 242(78.1%) participants were single and 62 (19.7%) were married, 166(53.45%) were from Punjab, 80(25.8%) from the federally-administered tribal areas, 26(8.3%) from Khyber Pakhtunkhwa, 7(2.2%) from Sindh and 7(1.93%) from Balochistan. Group identification significantly increased advocacy (p<0.001). Perceived group normative support for polio vaccination also increased advocacy (p < 0.01) and was associated with a decrease in scepticism (p< 0.001). Group identification interacted with perceived group normative support for polio vaccination to increase advocacy of polio vaccination (p<0.05). CONCLUSIONS: Group identity was found to influence attitudes towards polio vaccination in Pakistan by increasing the persuasive impact of perceived group normative support for polio vaccination.

Polio by the Numbers-A Global Perspective.

BACKGROUND: Investments in national immunization programs and the Global Polio Eradication Initiative (GPEI) have resulted in substantial reductions in paralytic polio worldwide. However, cases prevented because of investments in immunization programs and GPEI remain incompletely characterized. METHODS: Using a global model that integrates polio transmission, immunity, and vaccine dynamics, we provide estimates of polio incidence and numbers of paralytic cases prevented. We compare the results with reported cases and estimates historically published by the World Health Organization. RESULTS: We estimate that the existence and use of polio vaccines prevented 5 million cases of paralytic polio for 1960-1987 and 24 million cases worldwide for 1988-2021 compared to a counterfactual world with no polio vaccines. Since the 1988 resolution to eradicate polio, our estimates suggest GPEI prevented 2.5-6 million cases of paralytic polio compared to counterfactual worlds without GPEI that assume different levels of intensity of polio vaccine use in routine immunization programs. CONCLUSIONS: Analysis of historical cases provides important context for understanding and communicating the benefits of investments made in polio eradication. Prospective studies will need to explore the expected benefits of future investments, the outcomes of which will depend on whether and when polio is globally eradicated.

The Excluded Voices from Africa's Sahel: Alternative Meanings of Health in Narratives of Resistance to the Global Polio Eradication Initiative in Northern Nigeria.

Although previous inquiry into resistance to the polio vaccines in northern Nigeria has been launched from several disciplines, inquiry has been limited to the 2003 revolt and has rarely been informed by theory. This study drew on the culture-centered approach to health communication to argue that the exclusion of marginalized communities from decision-making by the Global Polio Eradication Initiative (GPEI) resulted in a vaccine resistance which found expression in health activism that engaged the local news media. To recover the excluded voices, this study examined community members' narratives of resistance to the vaccines in Nigerian news from 2012 to 2018. Upon providing a backdrop for these narratives through a chronology of GPEI milestones in northern Nigeria developed from Nigerian newspapers, the study then engaged with 168 speech acts of resistance in Nigerian news to co-construct alternative meanings of health. Drawing on a local cultural meaning of the vaccines as covertly carrying out a Western family-planning agenda, narrators negligibly associated "family planning" with health. Narrators further articulated health as access to foods and as religious practice. These findings have implications for the inclusion of voices from sub-Saharan Africa in GPEI decision-making.

Lessons from the elimination of poliomyelitis in Africa.

In August 2020, Africa was declared free of poliomyelitis (polio), bringing to fruition a goal that took more than 30 years to achieve. This Perspective chronicles global, continental, national and community actions taken by diverse stakeholders that finally led to the elimination of transmission of wild poliovirus in Africa. The cascade of events started with the development of polio vaccines and the realization that polio, much like smallpox, could be eradicated. After a 1988 pledge by the World Health Assembly to eradicate polio globally, concerted and deliberate efforts were made in Africa to achieve this goal. This included the use of evidence-based approaches for the harmonization and standardization of public health strategies, using a network of polio laboratories and emergency operation centres and actively pursuing underserved populations. Innovative solutions to counter challenges such as conflict and vaccine hesitancy may be of use in future public health interventions.

Routine Vaccination Coverage - Worldwide, 2020.

Endorsed by the World Health Assembly in 2020, the Immunization Agenda 2030 (IA2030) strives to reduce morbidity and mortality from vaccine-preventable diseases across the life course (1). This report, which updates a previous report (2), presents global, regional,* and national vaccination coverage estimates and trends as of 2020. Changes are described in vaccination coverage and the numbers of unvaccinated and undervaccinated children as measured by receipt of the first and third doses of diphtheria, tetanus, and pertussis-containing vaccine (DTP) in 2020, when the COVID-19 pandemic began, compared with 2019. Global estimates of coverage with the third dose of DTP (DTP3) and a polio vaccine (Pol3) decreased from 86% in 2019 to 83% in 2020. Similarly, coverage with the first dose of measles-containing vaccine (MCV1) dropped from 86% in 2019 to 84% in 2020. The last year that coverage estimates were at 2020 levels was 2009 for DTP3 and 2014 for both MCV1 and Pol3. Worldwide, 22.7 million children (17% of the target population) were not vaccinated with DTP3 in 2020 compared with 19.0 million (14%) in 2019. Children who did not receive the first DTP dose (DTP1) by age 12 months (zero-dose children) accounted for 95% of the increased number. Among those who did not receive DTP3 in 2020, approximately 17.1 million (75%) were zero-dose children. Global coverage decreased in 2020 compared with 2019 estimates for the completed series of Haemophilus influenzae type b (Hib), hepatitis B vaccine (HepB), human papillomavirus vaccine (HPV), and rubella-containing vaccine (RCV). Full recovery from COVID-19-associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks (3).