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Human Vaccines & Immunotherapeutics Dec 2024This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.
This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.
Topics: Humans; Infant; Antibodies, Neutralizing; Antibodies, Viral; China; Immunogenicity, Vaccine; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 38509699
DOI: 10.1080/21645515.2024.2324538 -
The Journal of General Virology Jun 2023Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and...
Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation.We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilized virus-like particles (VLPs) in .The stabilized VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilization, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralize virus . Therefore, anti-EVA71 neutralizing antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responses remains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies.
Topics: Child; Humans; Child, Preschool; Enterovirus; Enterovirus Infections; Antigens, Viral; Vaccines; Poliovirus; Antibodies, Viral
PubMed: 37390009
DOI: 10.1099/jgv.0.001867 -
Lancet (London, England) Jan 2023Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2)... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of the safety, immunogenicity, and faecal shedding of novel oral polio vaccine type 2 in healthy newborn infants in Bangladesh: a randomised, controlled, phase 2 clinical trial.
BACKGROUND
Type 2 circulating vaccine-derived polioviruses (cVDPV2) from Sabin oral poliovirus vaccines (OPVs) are the leading cause of poliomyelitis. A novel type 2 OPV (nOPV2) has been developed to be more genetically stable with similar tolerability and immunogenicity to that of Sabin type 2 vaccines to mitigate the risk of cVDPV2. We aimed to assess these aspects of nOPV2 in poliovirus vaccine-naive newborn infants.
METHODS
In this randomised, double-blind, controlled, phase 2 trial we enrolled newborn infants at the Matlab Health Research Centre, Chandpur, Bangladesh. We included infants who were healthy and were a single birth after at least 37 weeks' gestation. Infants were randomly assigned (2:1) to receive either two doses of nOPV2 or placebo, administered at age 0-3 days and at 4 weeks. Exclusion criteria included receipt of rotavirus or any other poliovirus vaccine, any infection or illness at the time of enrolment (vomiting, diarrhoea, or intolerance to liquids), diagnosis or suspicion of any immunodeficiency disorder in the infant or a close family member, or any contraindication for venipuncture. The primary safety outcome was safety and tolerability after one and two doses of nOPV2, given 4 weeks apart in poliovirus vaccine-naive newborn infants and the primary immunogenicity outcome was the seroconversion rate for neutralising antibodies against type 2 poliovirus, measured 28 days after the first and second vaccinations with nOPV2. Study staff recorded solicited and unsolicited adverse events after each dose during daily home visits for 7 days. Poliovirus neutralising antibody responses were measured in sera drawn at birth and at age 4 weeks and 8 weeks. This study is registered on ClinicalTrials.gov, NCT04693286.
FINDINGS
Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to receive nOPV2 (n=220 [67%]) or placebo (n=110 [33%]). nOPV2 was well tolerated; 154 (70%) of 220 newborn infants in the nOPV2 group and 78 (71%) of 110 in the placebo group had solicited adverse events, which were all mild or moderate in severity. Severe unsolicited adverse events in 11 (5%) vaccine recipients and five (5%) placebo recipients were considered unrelated to vaccination. 306 (93%) of 330 infants had seroprotective maternal antibodies against type 2 poliovirus at birth, decreasing to 58 (56%) of 104 in the placebo group at 8 weeks. In the nOPV2 group 196 (90%) of 217 infants seroconverted by week 8 after two doses, when 214 (99%) had seroprotective antibodies.
INTERPRETATION
nOPV2 was well tolerated and immunogenic in newborn infants, with two doses, at birth and 4 weeks, resulting in almost 99% of infants having protective neutralising antibodies.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Infant, Newborn; Humans; Infant; Child, Preschool; Bangladesh; Antibodies, Viral; Poliovirus Vaccine, Oral; Poliovirus; Poliomyelitis; Antibodies, Neutralizing; Double-Blind Method
PubMed: 36495882
DOI: 10.1016/S0140-6736(22)02397-2 -
Risk Analysis : An Official Publication... Feb 2021Nearly 20 years after the year 2000 target for global wild poliovirus (WPV) eradication, live polioviruses continue to circulate with all three serotypes posing...
Nearly 20 years after the year 2000 target for global wild poliovirus (WPV) eradication, live polioviruses continue to circulate with all three serotypes posing challenges for the polio endgame. We updated a global differential equation-based poliovirus transmission and stochastic risk model to include programmatic and epidemiological experience through January 2020. We used the model to explore the likely dynamics of poliovirus transmission for 2019-2023, which coincides with a new Global Polio Eradication Initiative Strategic Plan. The model stratifies the global population into 72 blocks, each containing 10 subpopulations of approximately 10.7 million people. Exported viruses go into subpopulations within the same block and within groups of blocks that represent large preferentially mixing geographical areas (e.g., continents). We assign representative World Bank income levels to the blocks along with polio immunization and transmission assumptions, which capture some of the heterogeneity across countries while still focusing on global poliovirus transmission dynamics. We also updated estimates of reintroduction risks using available evidence. The updated model characterizes transmission dynamics and resulting polio cases consistent with the evidence through 2019. Based on recent epidemiological experience and prospective immunization assumptions for the 2019-2023 Strategic Plan, the updated model does not show successful eradication of serotype 1 WPV by 2023 or successful cessation of oral poliovirus vaccine serotype 2-related viruses.
Topics: Disease Eradication; Disease Outbreaks; Global Health; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Risk Assessment; Risk Management; Vaccination
PubMed: 31960533
DOI: 10.1111/risa.13447 -
Virologie (Montrouge, France) Jun 2023The genus Enterovirus (family Picornaviridae) contains numerous viruses, most of which have been identified in humans. Among them, the three serotypes of poliovirus,... (Review)
Review
The genus Enterovirus (family Picornaviridae) contains numerous viruses, most of which have been identified in humans. Among them, the three serotypes of poliovirus, coxsackieviruses A and B, echoviruses, rhinoviruses and other enteroviruses (EVs) responsible in humans for a wide spectrum of clinical manifestations. There are also 60 identified EVs in different mammals. Some have been found in both humans and animals, demonstrating the possibility of zoonotic transmission of certain EVs. Compared to human EVs, genetic and epidemiological data for animal EVs are scarce. However, the detection of EV in various species of mammals and their presence on all continents suggest that the number of EV still to be discovered is very important. Some EVs found in animals have characteristics never seen in human EVs. Furthermore, the unique phylogenetic relationships observed between animal EVs raise interesting questions about the rules that govern the evolution of these viruses. The aim of this review is to present the salient data on animal EVs and to highlight the questions they raise.
Topics: Animals; Humans; Phylogeny; Enterovirus; Enterovirus Infections; Poliovirus; Enterovirus B, Human; Mammals
PubMed: 37462933
DOI: 10.1684/vir.2023.0999 -
The Lancet. Microbe Dec 2022Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to...
Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials.
BACKGROUND
Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks.
METHODS
In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model.
FINDINGS
Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log 50% cell culture infectious dose (CCID) and 76·7% at the 5 log CCID inoculum levels, with rates of 2·8% for 4 log CCID and 11·8% for 5 log CCID observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients.
INTERPRETATION
The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Mice; Animals; Poliovirus; Poliomyelitis; Poliovirus Vaccine, Oral; 5' Untranslated Regions; Mice, Transgenic; Paralysis; Nucleotides
PubMed: 36332645
DOI: 10.1016/S2666-5247(22)00254-3 -
Viruses Jul 2021The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global... (Review)
Review
The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global polio eradication. However, polio outbreaks, mainly caused by type 2 circulating vaccine-derived poliovirus (cVDPV2), are increasing worldwide. Meanwhile, immunodeficiency-associated vaccine-derived poliovirus (iVDPV) is considered another risk factor during the final stage of global polio eradication. Patients with primary immunodeficiency diseases are associated with higher risks for long-term iVDPV infections. Although a limited number of chronic iVDPV excretors were reported, the recent identification of a chronic type 2 iVDPV (iVDPV2) excretor in the Philippines highlights the potential risk of inapparent iVDPV infection for expanding cVDPV outbreaks. Further research on the genetic characterizations and molecular evolution of iVDPV2, based on comprehensive iVDPV surveillance, will be critical for elucidating the remaining risk of iVDPV2 during the post-OPV era.
Topics: Disease Eradication; Disease Outbreaks; Evolution, Molecular; Global Health; Humans; Immunocompromised Host; Poliovirus; Poliovirus Vaccine, Oral; Primary Immunodeficiency Diseases; Vaccination
PubMed: 34372613
DOI: 10.3390/v13071407 -
Vaccine Apr 2021A domestic Sabin strain-based inactivated poliovirus vaccine (Sabin IPV) was approved by China Food and Drug Administration in 2017 as a replacement for the Salk... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of sabin-strain based inactivated poliovirus vaccine replacing salk-strain based inactivated poliovirus vaccine: An innovative application of different strain-IPVs replacement.
BACKGROUND
A domestic Sabin strain-based inactivated poliovirus vaccine (Sabin IPV) was approved by China Food and Drug Administration in 2017 as a replacement for the Salk strain-based inactivated poliovirus vaccine (Salk IPV) that has been in use in China for over 10 years. The present post-marketing trial was implemented in China to assess the immunogenicity and safety of replacing the Salk IPV with the Sabin IPV in the last two immunizations of the standard three-dose schedule.
METHODS
We conducted a randomized, controlled clinical trial with two groups that received three doses of IPVs at the age of 2, 3, and 4 months: the Salk-Sabin-Sabin group and the Salk-Salk-Salk group. Blood samples were collected before vaccination and 30-40 days after the third dose of vaccination. The seroconversion rates and antibody geometric mean titers (GMTs) were calculated and analyzed to evaluate immunogenicity. The safety of both immunization schedules was also monitored and analyzed.
RESULTS
Of 360 recruited healthy infants, all three IPV doses were administered and blood collection was completed in 330 infants. All participants (100%) in both groups were seropositive for all three poliovirus types after the last vaccination. There were significant differences between the two groups (P < 0.001) in the GMTs for antibodies against poliovirus types 1 and 2, but no significant difference was observed for antibodies against type 3 (P = 0.009). A non-inferiority t-test showed that the post-immunization GMTs for all three types in the Salk-Sabin-Sabin group were not inferior to those in the Salk-Salk-Salk group (P < 0.001). Safety assessment indicated that there was no significant difference in the incidence of all adverse events between the two groups (P = 0.806).
CONCLUSIONS
The Salk-Sabin-Sabin IPV immunization schedule is not inferior to the Salk-Salk-Salk IPV schedule in terms of both immunogenicity and safety. Clinical trial number: NCT04051736.
Topics: Antibodies, Viral; China; Humans; Immunization Schedule; Immunogenicity, Vaccine; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 33810904
DOI: 10.1016/j.vaccine.2021.02.073 -
Journal of Virology Dec 2019Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of...
Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota. Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.
Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bacteria; Coxsackievirus Infections; Disease Models, Animal; Enterovirus; Enterovirus Infections; HeLa Cells; Humans; Male; Mice; Mice, Inbred C57BL; Microbiota; Picornaviridae; Poliovirus; Vancomycin; Virus Replication
PubMed: 31511379
DOI: 10.1128/JVI.01339-19 -
The Pan African Medical Journal 2023in 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...
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.
Topics: Child; Humans; Poliovirus; Nigeria; Population Surveillance; Poliomyelitis; Poliovirus Vaccines; Poliovirus Vaccine, Oral; Immunization Programs; Disease Eradication
PubMed: 38370099
DOI: 10.11604/pamj.supp.2023.45.2.38079