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Further development of a new transgenic mouse test for the evaluation of the immunogenicity and protective properties of inactivated poliovirus vaccine.

Recently, we developed and optimized a new method for the evaluation of the protective properties of serotype 2 inactivated poliovirus vaccines (IPV). The method is based on the immunization and subsequent challenge of transgenic (Tg) mice susceptible to poliovirus. We describe a similar method for the assessment of the protectiveness of serotype 1 IPV and demonstrate that experimental IPV produced from attenuated Sabin strain (sIPV) of serotype 1 poliovirus induced serum neutralizing antibodies, immunoglobulin (Ig) G, IgM, and salivary IgA at titers comparable to those induced by conventional…

Evaluation of immunogenicity and protective properties of inactivated poliovirus vaccines: a new surrogate method for predicting vaccine efficacy.

An assay for the evaluation of protective properties of inactivated poliovirus vaccines (IPVs) in transgenic (Tg) mice susceptible to poliovirus has been developed and optimized for type 2 IPV. This method was used to compare the immunogenicity and protective properties of experimental IPV produced from the attenuated Sabin strain (sIPV) with those of conventional IPV (cIPV) produced from the wild-type (wt) poliovirus MEF-1 strain. Modified enzyme-linked immunosorbent assays (ELISAs) were used to measure immune response in serum and saliva samples from test mice. Tg mice were vaccinated and we…

Inhibition of poliovirus RNA synthesis as a molecular mechanism contributing to viral persistence in the mouse central nervous system.

Many survivors of poliomyelitis, several decades after the acute phase of the disease, develop a set of new muscle symptoms called post-polio syndrome. The persistence of poliovirus (PV) in the central nervous system (CNS) may be involved in the aetiology of this syndrome. By using a mouse model, we have shown that PV persists in the CNS of paralysed mice for over a year after the acute disease. Detection of PV plus- and minus-strand RNAs in the spinal cord of paralysed mice suggested continuous PV RNA replication in the CNS. However, infectious PV particles could not be recovered from homogen…

Neurologic complications associated with oral poliovirus vaccine and genomic variability of the vaccine strains after multiplication in humans.

The oral poliovirus vaccine (OPV) has been effectively used in the reduction and control of poliomyelitis cases on the planet. Despite several advantages of using the attenuated OPV strains, the rare occurrence of vaccine-associated paralytic poliomyelitis (VAPP) cases in vaccine recipients and their susceptible contacts is a disadvantage. Molecular biology studies of polioviruses isolated from stool and central nervous system (CNS) of patients with VAPP have confirmed the vaccine origin of the isolates and demonstrated genomic modifications known or suspected to increase the neurovirulence. S…

Seroprevalence of antibody against poliovirus in inner-city preschool children. Implications for vaccination policy in the United States.

OBJECTIVES: To assess susceptibility to poliomyelitis in selected inner-city preschool children in the United States and to estimate the contribution of secondary spread of live attenuated oral poliovirus vaccine virus to type-specific immunity. DESIGN: Cross-sectional seroprevalence study. METHODS: Serum neutralizing antibody levels against poliovirus types 1, 2, and 3 were analyzed according to vaccination status, age, and other sociodemographic variables. SETTING: Hospital and satellite clinics serving inner-city populations in Houston, Tex, and Detroit, Mich, 1990 to 1991. PARTICIPANTS…

Final checkpoint in the drug-promoted and poliovirus-promoted apoptosis is under post-translational control by growth factors.

The treatment of HeLa subline (HeLa-B) cells with cycloheximide or Actinomycin D resulted in a rapid (approximately 1.5 h and approximately 2.5 h, respectively) development of morphological and biochemical signs of apoptosis. The addition of fetal bovine serum to the cycloheximide-treated or Actinomycin D-treated cells suppressed the apoptotic reaction, as evidenced by the postponement of the DNA fragmentation for at least 9 and 5 h, respectively. A similar suppressive effect was observed upon the serum addition to cells undergoing abortive infection with poliovirus, which died of apoptosis in…

Possible influence of measles virus infection of cynomolgus monkeys on the outcome of the neurovirulence test for oral poliovirus vaccine.

Macaque monkeys are susceptible to measles infection which triggers temporary immuno-depression similar to the well known phenomenon in humans. It is known that feral monkeys become infected with measles virus when they are exposed to humans. Since Macaca mulatta and M. fascicularis are species used to assay the neurovirulence of oral poliovirus vaccine, the immunodepression caused by measles infection of the test monkeys could significantly alter the results of the neurovirulence test. The serum titers of measles-neutralizing antibodies were studied in over 1500 monkeys used for neurovirulenc…

Community surveillance after detection of poliovirus in the environment in London, United Kingdom, October 2022 to April 2023.

BackgroundVaccine-derived polioviruses (VDPVs) continue to circulate internationally, causing sporadic cases and outbreaks of paralytic polio in countries certified as polio-free. In 2022, sustained detection of type 2 VDPVs was reported in environmental surveillance samples collected from London. Genetic mutations indicative of loss of attenuation of virulence were observed, consistent with community transmission events over several months.AimWe aimed to determine the extent of geographical spread of transmission in an area of environmental poliovirus detection.MethodsWe implemented an opport…

Certifying the interruption of wild poliovirus transmission in the WHO African region on the turbulent journey to a polio-free world.

On Aug 25 2020, the Africa Regional Commission for the Certification of Poliomyelitis Eradication declared that the WHO African region had interrupted transmission of all indigenous wild polioviruses. This declaration marks the African region as the fifth of the six WHO regions to celebrate this extraordinary achievement. Following the Yaoundé Declaration on Polio Eradication in Africa by heads of state and governments in 1996, Nelson Mandela launched the Kick Polio out of Africa campaign. In this Health Policy paper, we describe the long and turbulent journey to the certification of the inter…

Vaccine schedules and the effect on humoral and intestinal immunity against poliovirus: a systematic review and network meta-analysis.

BACKGROUND: The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules. METHODS: We did a random-effect meta-analysis with single proportions and a network meta-analysis in a …

Population sensitivity of acute flaccid paralysis and environmental surveillance for serotype 1 poliovirus in Pakistan: an observational study.

BACKGROUND: To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation. METHODS: Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surv…

Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry.

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in…

A Supply and Demand Management Perspective on the Accelerated Global Introductions of Inactivated Poliovirus Vaccine in a Constrained Supply Market.

A total of 105 countries have introduced IPV as of September 2016 of which 85 have procured the vaccine through UNICEF. The Global Eradication and Endgame Strategic Plan 2013-2018 called for the rapid introduction of at least one dose of IPV into routine immunization schedules in 126 all OPV-using countries by the end of 2015. At the time of initiating the procurement process, demand was estimated based on global modeling rather than individual country indications. In its capacity as procurement agency for the Global Polio Eradication Initiative and Gavi, the Vaccine Alliance, UNICEF set out t

Modeling strategies to increase population immunity and prevent poliovirus transmission in the high-risk area of northwest Nigeria.

BACKGROUND: Nigeria continues to struggle in its efforts to eliminate circulating live polioviruses using oral poliovirus vaccine (OPV). METHODS: We modeled population immunity, and we estimated cases and the timing of transmission die-out for numerous policies that could accelerate the elimination of wild poliovirus type 1 (WPV1) and help Nigeria manage the risks of circulating vaccine-derived polioviruses (cVDPVs). We used a differential-equation based poliovirus transmission and OPV evolution model focused on northwest Nigeria to characterize the impact and trade-offs of potential vaccinat…

Population immunity to polioviruses in the context of a large-scale wild poliovirus type 1 outbreak in Tajikistan, 2010.

BACKGROUND: A serosurvey to evaluate population immunity to polioviruses (PVs) in the context of the importation-related wild PV1 outbreak in Tajikistan in 2010 (461 confirmed cases among children and young adults) was conducted. METHODS: Serum specimens from a nationwide sample of 1-24 year-old persons selected through stratified cluster sampling (n=2447) were tested for neutralizing antibodies to all three PV types. Samples with titers<1:8 were considered seronegative. The serosurvey was conducted during the interval after mOPV1 supplementary immunization activities (SIAs) and before tOPV S…

Риски, связанные с использованием привитых вживую штаммов полиомиелитвируса и стратегиями борьбы с паралитическим полиомиелитом и его искоренения.

Глобальная инициатива по искоренению полиомиелита была выдвинута в 1988 году с целью ликвидации паралитического полиомиелита. Имеются две эффективные вакцины: неактивированная вакцина против полиомиелита (ВПВ) и пероральная вакцина от полиомиелита (ОВП). С 1964 года OPV используется вместо IPV в большинстве стран благодаря нескольким экономическим и биологическим преимуществам. Вместе с тем в редких случаях живые штаммы сабина ОПВ возвращаются к нейровинулентности и вызывают паралитический полиомиелит, связанный с вакцинами, в вакцинах или приводят к появлению штаммов полиомиелита, полученных

Совпадение в аннотации оригинала
The Global Polio Eradication Initiative was launched in 1988 with the aim to eliminate paralytic poliomyelitis. Two effective vaccines are a … use vaccine-associated paralytic poliomyelitis in vaccinees or lead to emergence of vaccine-derived poliovirus strains. Attenuating mutations and recombination events have been associated with the reversion of vaccine strains to neurovirulence. The substitution of OPV with an improved new-generation IPV and the availability of new specific drugs against poli …

Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model.

BACKGROUND: It is accepted that oral poliovirus vaccine (OPV) can cause vaccine-associated paralytic poliomyelitis (VAPP) and that wild poliovirus infection can rarely present as transverse myelitis. It is therefore possible that OPV could cause transverse myelitis. We previously reported a case of transverse myelitis that developed in a 6-month-old boy, 7 days after receiving his second dose of OPV. OBJECTIVES: Our aim was to test the virus from this patient with transverse myelitis for neurovirulence in a mouse model. STUDY DESIGN: The TgPVR21 transgenic mouse line, which expresses the hum…

Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine.

Production of live attenuated oral poliomyelitis vaccine (OPV) requires rigorous neurovirulence safety testing of each vaccine lot, currentl … kidney cells that are used for manufacturing of the vaccine. We have also found that the wild-type poliovirus type 3 strain Leon/37, from which the vaccine strain was originally derived, contained a mixture of 472-U and 472-C sequences. No other mutations in OPV type 3 RNA have been detected by similar assays at position 2034, also associated with attenuati …