Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses.
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ABSTRACT:
SUBMITTER: Wahid R
PROVIDER: S-EPMC8322168 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.
| S-EPMC6991977 | biostudies-literature
Project description:Six different adjuvants, each in combination with inactivated polio vaccine (IPV) produced with attenuated Sabin strains (sIPV), were evaluated for their ability to enhance virus neutralizing antibody titres (VNTs) in the rat potency model. The increase of VNTs was on average 3-, 15-, 24-fold with adjuvants after one immunization (serotypes 1, 2, and 3, respectively). Also after a boost immunization the VNTs of adjuvanted sIPV were on average another 7-20-27 times higher than after two inoculations of sIPV without adjuvant. The results indicate that it is feasible to increase the potency of inactivated polio vaccines by using adjuvants.
| S-EPMC3570672 | biostudies-literature
Project description:From 2001 to 2004, Switzerland switched from routine vaccination with oral polio vaccine (OPV) to inactivated polio vaccine (IPV), using both vaccines in the intervening period. Since IPV is less effective at inducing mucosal immunity than OPV, this change might allow imported poliovirus to circulate undetected more easily in an increasingly IPV-immunized population. Environmental monitoring is a recognized tool for identifying polioviruses in a community. To look for evidence of poliovirus circulation following cessation of OPV use, two sewage treatment plants located in the Zurich area were sampled from 2004 to 2006. Following virus isolation using either RD or L20B cells, enteroviruses and polioviruses were identified by reverse transcription-PCR. A total of 20 out of 174 wastewater samples were positive for 62 Sabin-like isolates. One isolate from each poliovirus-positive sample was analyzed in more detail. Sequencing the complete viral protein 1 (VP1) capsid coding region, as well as intratypic differentiation (ITD), identified 3 Sabin type 1, 13 Sabin type 2, and 4 Sabin type 3 strains. One serotype 1 strain showed a discordant result in the ITD. Three-quarters of the strains showed mutations within the 5' untranslated region and VP1, known to be associated with reversion to virulence. Moreover, three strains showed heterotypic recombination (S2/S1 and S3/S2/S3). The low number of synonymous mutations and the partial temperature sensitivity are not consistent with extended circulation of these Sabin virus strains. Nevertheless, the continuous introduction of polioviruses into the community emphasizes the necessity for uninterrupted child vaccination to maintain high herd immunity.
| S-EPMC2547022 | biostudies-literature
Project description:BackgroundWe present an empirical economic cost analysis of the April 2016 switch from trivalent (tOPV) to bivalent (bOPV) oral polio vaccine at the national-level and 3 provinces (Bali, West Sumatera and Nusa Tenggara) for Indonesia's Expanded Program on Immunization.MethodsData on the quantity and prices of resources used in the 4 World Health Organization guideline phases of the switch were collected at the national-level and in each of the sampled provinces, cities/districts, and health facilities. Costs were calculated as the sum of the value of resources reportedly used in each sampled unit by switch phase.ResultsEstimated national-level costs were $46 791. Costs by health system level varied from $9062 to $34 256 at the province-level, from $4576 to $11 936 at the district-level , and from $3488 to $29 175 at the city-level. Estimated national costs ranged from $4 076 446 (Bali, minimum cost scenario) to $28 120 700 (West Sumatera, maximum cost scenario).ConclusionsOur findings suggest that the majority of tPOV to bOPV switch costs were borne at the subnational level. Considerable variation in reported costs among health system levels surveyed indicates a need for flexibility in budgeting for globally synchronized public health activities.
| S-EPMC5853418 | biostudies-literature
Project description:Background:Understanding the spatial dynamics of oral polio vaccine (OPV) transmission will improve resource targeting. Mexico provides a natural laboratory, as it uses inactivated polio vaccine routinely as well as OPV bi-annually. Methods:Using geospatial maps, we measured the distance and density of OPV vaccinees' shedding in the areas nearest to unvaccinated households in 3 Mexican villages. Comparison of transmission to unvaccinated households utilized a mixed effects logistic regression with random effects for household and time, adjusted for age, gender, area, and running water. Results:The median distance from an unvaccinated household to its nearest OPV-shedding household was 85 meters (interquartile range, 46-145) and the median number of vaccinees shedding OPV within 200 m was 3 (2-6). Transmission to unvaccinated households occurred by day 1. There was no association (odds ratio [OR] 1.04; 95% credible interval [CrI] 0.92-1.16) between the distance from OPV shedding and the odds of transmission. The number of OPV vaccinees shedding within 200 m came close to a significant association with unvaccinated transmission (OR 0.93; CrI 0.84-1.01), but this was not the case for households 100 or 500 m apart. Results were consistent across the 3 villages. Conclusions:Geospatial analysis did not predict community transmission from vaccinated to unvaccinated households, because OPV use resulted in rapid, low transmission levels. This finding supports the global cessation of OPV.
| S-EPMC6206123 | biostudies-literature
Project description:Launched in 1988, the Global Polio Eradication Initiative (GPEI) aims to eradicate polioviruses, which are the etiologic agents of poliomyelitis. Coordinated by the World Health Organization, this program relies on two pillars: mass vaccination campaigns that target children and active surveillance of the virus circulation. The GPEI has led to the eradication of two out of three serotypes of wild polioviruses and to the containment of the last serotype in two countries.Two polio vaccines exist: the injectable vaccine and the oral one. Both induce an efficient protection against poliomyelitis, but only the oral vaccine is able to stop poliovirus transmission chains. Therefore, the oral vaccine is essential to contain polioviruses and, finally, to eradicate them. In some contexts where the vaccine coverage is not sufficient, the attenuated strains contained in the oral vaccine can circulate for months and recover a pathogenic phenotype through genetic drift. In order to prevent this phenomenon, a new vaccine strain has been developed through genetic engineering: it has been designed to be as immunogenic as the historical vaccine strain, but more genetically stable to prevent the loss of its attenuation determinants. After being evaluated in vitro and through clinical trials, the novel strain has been rolled out in several African countries and in Tajikistan in 2021.
| S-EPMC9283809 | biostudies-literature
Project description:The oral polio vaccine (OPV) contains live-attenuated polioviruses that induce immunity by causing low virulence infections in vaccine recipients and their close contacts. Widespread immunization with OPV has reduced the annual global burden of paralytic poliomyelitis by a factor of 10,000 or more and has driven wild poliovirus (WPV) to the brink of eradication. However, in instances that have so far been rare, OPV can paralyze vaccine recipients and generate vaccine-derived polio outbreaks. To complete polio eradication, OPV use should eventually cease, but doing so will leave a growing population fully susceptible to infection. If poliovirus is reintroduced after OPV cessation, under what conditions will OPV vaccination be required to interrupt transmission? Can conditions exist in which OPV and WPV reintroduction present similar risks of transmission? To answer these questions, we built a multi-scale mathematical model of infection and transmission calibrated to data from clinical trials and field epidemiology studies. At the within-host level, the model describes the effects of vaccination and waning immunity on shedding and oral susceptibility to infection. At the between-host level, the model emulates the interaction of shedding and oral susceptibility with sanitation and person-to-person contact patterns to determine the transmission rate in communities. Our results show that inactivated polio vaccine (IPV) is sufficient to prevent outbreaks in low transmission rate settings and that OPV can be reintroduced and withdrawn as needed in moderate transmission rate settings. However, in high transmission rate settings, the conditions that support vaccine-derived outbreaks have only been rare because population immunity has been high. Absent population immunity, the Sabin strains from OPV will be nearly as capable of causing outbreaks as WPV. If post-cessation outbreak responses are followed by new vaccine-derived outbreaks, strategies to restore population immunity will be required to ensure the stability of polio eradication.
| S-EPMC5942853 | biostudies-literature
Project description:BackgroundEffective response to emerging pandemic threats is complicated by the need to develop specific vaccines and other medical products. The availability of broadly specific countermeasures that could be deployed early in the pandemic could significantly alter its course and save countless lives. Live attenuated vaccines (LAVs) were shown to induce non-specific protection against a broad spectrum of off-target pathogens by stimulating innate immune responses. The purpose of this study was to evaluate the effect of immunization with bivalent Oral Poliovirus Vaccine (bOPV) on the incidence of COVID-19 and other acute respiratory infections (ARIs).Methods and findingsA randomized parallel-group comparative study was conducted in Kirov Medical University. 1115 healthy volunteers aged 18 to 65 were randomized into two equal groups, one of which was immunized orally with a single dose of bOPV "BiVac Polio" and another with placebo. The study participants were monitored for three months for respiratory illnesses including COVID-19. The endpoint was the incidence of acute respiratory infections and laboratory confirmed COVID-19 in both groups during 3 months after immunization. The number of laboratory-confirmed cases of COVID-19 was significantly lower in the vaccinated group than in placebo (25 cases vs. 44, p=0.036). The difference between the overall number of clinically diagnosed respiratory illnesses in the two groups was not statistically significant.ConclusionsImmunization with bOPV reduced the number of laboratory-confirmed COVID-19 cases, consistent with the original hypothesis that LAVs induce non-specific protection against off-target infections. The findings are in line with previous observations of the protective effects of OPV against seasonal influenza and other viral and bacterial pathogens. The absence of a statistically significant effect on the total number of ARIs may be due to the insufficient number of participants and heterogeneous etiology of ARIs. OPV could be used to complement specific coronavirus vaccines, especially in regions of the world where the vaccines are unavailable, and as a stopgap measure for urgent response to future emerging infections. Clinical trial registration number NCT05083039 at clinicaltrals.gov https://clinicaltrials.gov/ct2/show/NCT05083039?term=NCT05083039&draw=2&rank=1.
| S-EPMC9196174 | biostudies-literature
Project description:BackgroundQuantifying interference of maternal antibodies with immune responses to varying dose schedules of inactivated polio vaccine (IPV) is important for the polio endgame as IPV replaces oral polio vaccine (OPV).MethodsType 2 poliovirus humoral and intestinal responses were analyzed using pre-IPV type 2 seropositivity as proxy for maternal antibodies from 2 trials in Latin America. Infants received 1 or 2 doses of IPV in sequential IPV-bivalent oral polio vaccine (bOPV) or mixed bOPV-IPV schedules.ResultsAmong infants vaccinated with bOPV at age 6, 10, and 14 weeks of age and IPV at 14 weeks, those with type 2 pre-IPV seropositivity had lower seroprotection rates than seronegative infants at 4 weeks (92.7% vs 83.8%; difference, 8.9% [95% confidence interval, 0.6%-19.9%]; n = 260) and 22 weeks (82.7% vs 60.4%; difference, 22.3 [12.8%-32.4%]; n = 481) post-IPV. A second IPV at age 36 weeks resulted in 100% seroprotection in both groups. Among infants vaccinated with 1 IPV at age 8 weeks followed by 2 doses of bOPV, pre-IPV type 2-seropositive infants had lower seroprotection at age 28 weeks than those who were seronegative (93.0% vs 73.9%; difference, 19.6% [95% confidence interval, 7.3%-29.4%]; n = 168). A second dose of IPV at 16 weeks achieved >97% seroprotection at age 24 or 28 weeks, regardless of pre-IPV status. Poliovirus shedding after challenge with monovalent OPV, serotype 2, was higher in pre-IPV seropositive infants given sequential IPV-bOPV. No differences were observed in the mixed bOPV-IPV schedule.ConclusionsThe presence of maternal antibody is associated with lower type 2 post-IPV seroprotection rates among infants who receive a single dose of IPV. This impact persists until late in infancy and is overcome by a second IPV dose.
| S-EPMC6206111 | biostudies-literature
Project description:BackgroundImmunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.MethodsPolio neutralizing antibody assays were conducted at 7 and 15?months of age for serotypes 1 and 3. Analyses were conducted on children receiving ?3 OPV doses (n?=?1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log2(titer)?<?3] and Log2(titer) by serotype using multivariate regression.FindingsSerotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15?months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively; however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log2 titers by 0.34 (95% CI 0.14-0.54) and 0.53 (95% CI 0.29-0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6-5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15-1.43) and 1.23 (95% CI 0.34-2.12) higher serotype 1 and 3 Log2 titer, respectively, and a 0.04 (95% CI 0.002-0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response.InterpretationUnder real-world conditions, improved vaccination coverage and socio-environmental conditions, and reducing early life bacterial exposures are key to improving OPV response and should inform polio eradication strategies.
| S-EPMC6325791 | biostudies-literature