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Nature Communications Mar 2024Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a...
Many countries continue to experience pertussis epidemics despite widespread vaccination. Waning protection after booster vaccination has highlighted the need for a better understanding of the immunological factors that promote durable protection. Here we apply systems vaccinology to investigate antibody responses in adolescents in the Netherlands (N = 14; NL) and the United Kingdom (N = 12; UK) receiving a tetanus-diphtheria-acellular pertussis-inactivated poliovirus (Tdap-IPV) vaccine. We report that early antiviral and interferon gene expression signatures in blood correlate to persistence of pertussis-specific antibody responses. Single-cell analyses of the innate response identified monocytes and myeloid dendritic cells (MoDC) as principal responders that upregulate antiviral gene expression and type-I interferon cytokine production. With public data, we show that Tdap vaccination stimulates significantly lower antiviral/type-I interferon responses than Tdap-IPV, suggesting that IPV may promote antiviral gene expression. Subsequent in vitro stimulation experiments demonstrate TLR-dependent, IPV-specific activation of the pro-inflammatory p38 MAP kinase pathway in MoDCs. Together, our data provide insights into the molecular host response to pertussis booster vaccination and demonstrate that IPV enhances innate immune activity associated with persistent, pertussis-specific antibody responses.
Topics: Adolescent; Humans; Bordetella pertussis; Immunity, Humoral; Tetanus; Whooping Cough; Diphtheria; Vaccines, Combined; Antibodies, Bacterial; Diphtheria-Tetanus-acellular Pertussis Vaccines; Poliovirus Vaccine, Inactivated; Vaccination; Immunization, Secondary; Corynebacterium; Poliovirus; Interferons; Antiviral Agents
PubMed: 38459022
DOI: 10.1038/s41467-024-46560-w -
Journal of Virological Methods May 2024Polioviruses (PV), the main causative agent of acute flaccid paralysis (AFP), are positive-sense single-stranded RNA viruses of the family Picornaviridae. As we approach...
Polioviruses (PV), the main causative agent of acute flaccid paralysis (AFP), are positive-sense single-stranded RNA viruses of the family Picornaviridae. As we approach polio eradication, accurate and timely detection of poliovirus in stool from AFP cases becomes vital to success for the eradication efforts. Direct detection of PV from clinical diagnostic samples using nucleic acid (NA) extraction and real-time reverse transcriptase polymerase chain reaction (rRT-PCR) instead of the current standard method of virus isolation in culture, eliminates the long turn-around time to diagnosis and the need for high viral titer amplification in laboratories. An essential component of direct detection of PV from AFP surveillance samples is the efficient extraction of NA. Potential supply chain issues and lack of vendor presence in certain areas of the world necessitates the validation of multiple NA extraction methods. Using retrospective PV-positive surveillance samples (n=104), two extraction kits were compared to the previously validated Zymo Research Quick-RNA™ Viral Kit. The Roche High Pure Viral RNA Kit, a column-based manual extraction method, and the MagMaX™ Pathogen RNA/DNA kit used in the automated Kingfisher Flex system were both non-inferior to the Zymo kit, with similar rates of PV detection in pivotal rRT-PCR assays, such as pan-poliovirus (PanPV), poliovirus serotype 2 (PV2), and wild poliovirus serotype 1 (WPV1). These important assays allow the identification and differentiation of PV genotypes and serotypes and are fundamental to the GPLN program. Validation of two additional kits provides feasible alternatives to the current piloted method of NA extraction for poliovirus rRT-PCR assays.
Topics: Humans; Poliovirus; Retrospective Studies; alpha-Fetoproteins; Poliomyelitis; Enterovirus; RNA, Viral
PubMed: 38458353
DOI: 10.1016/j.jviromet.2024.114914 -
Le Infezioni in Medicina 2024After a long global battle with wild poliovirus, the virus has been defeated through researches and vaccination using the oral polio vaccine and inactivated polio...
After a long global battle with wild poliovirus, the virus has been defeated through researches and vaccination using the oral polio vaccine and inactivated polio vaccine as well as sensitization. The issue that is now of global concern is that of vaccine-derived poliovirus which emerged from the unstable oral polio vaccine. Ninety sewage water samples were collected from slums in Maiduguri using grab method, concentrated using two phase separation method and subjected to intratypic differentiation and vaccine-derived poliovirus screening. The result revealed the presence of Sabin 1in 17 samples (61.0%) and Sabin 3 in 22 samples (79.0%), all of which were positive after vaccine-derived poliovirus screening. The presence of strains of Sabin 1 and Sabin 3 in the sewage water samples collected is an indication of virus shedding in individuals which could be as a result of vaccination or contact with the faeces infected or vaccinated individuals.
PubMed: 38456020
DOI: 10.53854/liim-3201-12 -
NPJ Vaccines Feb 2024Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential...
Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.
PubMed: 38424078
DOI: 10.1038/s41541-024-00831-1 -
PloS One 2024Acute Flaccid Paralysis (AFP) surveillance is the gold standard in the polio eradication initiative. The environmental component of polio surveillance can detect...
BACKGROUND
Acute Flaccid Paralysis (AFP) surveillance is the gold standard in the polio eradication initiative. The environmental component of polio surveillance can detect circulating Polioviruses from sewage without relying on clinical presentation. The effectiveness of the Environmental Surveillance (ES) is crucial to global polio eradication. We assessed the usefulness and attributes of the ES system in the Northern region and determined if the system is meeting its objectives.
METHODS
We conducted a descriptive cross-sectional evaluation in the Northern region from 2019 to 2020 using the updated US Centers for Disease Control and Prevention guideline. We interviewed stakeholders, reviewed records, and observed surveillance activities from 29th March to 7th May, 2021. Quantitative data were analyzed manually as frequencies and proportions whiles thematic analysis was used for the qualitative data.
RESULTS
One of 48 (2.1%) samples collected tested positive for circulating vaccine-derived Poliovirus (cVDPV). The cVDPV detection triggered enhanced AFP surveillance that resulted in the identification of a case of AFP. Three rounds of polio vaccination campaigns were organized. All surveillance officers interviewed were willing to continue providing their services for the ES. Reporting form has few variables and is easy to complete. The completeness of forms was 97.9% (47/48). Samples collected were dispatched on the same day to the testing laboratory. The system's data was managed manually.
CONCLUSION
The system was useful in detecting polio outbreaks. Data quality was good, the system was simple, flexible, acceptable, representative, and fairly stable. Sensitivity was high but predictive value positive was low. Timeliness in reporting was good but feedback from the national level could not be assessed. There is a need to improve on the feedback system and ensure that, the surveillance data is managed electronically.
Topics: Humans; alpha-Fetoproteins; Cross-Sectional Studies; Environmental Monitoring; Ghana; Poliomyelitis; Poliovirus
PubMed: 38422061
DOI: 10.1371/journal.pone.0294305 -
Lancet (London, England) Mar 2024Novel oral poliovirus vaccine type 2 (nOPV2) has been engineered to improve the genetic stability of Sabin oral poliovirus vaccine (OPV) and reduce the emergence of... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety of the novel oral poliovirus vaccine type 2 (nOPV2) in infants and young children aged 1 to <5 years and lot-to-lot consistency of the immune response to nOPV2 in infants in The Gambia: a phase 3, double-blind, randomised controlled trial.
BACKGROUND
Novel oral poliovirus vaccine type 2 (nOPV2) has been engineered to improve the genetic stability of Sabin oral poliovirus vaccine (OPV) and reduce the emergence of circulating vaccine-derived polioviruses. This trial aimed to provide key safety and immunogenicity data required for nOPV2 licensure and WHO prequalification.
METHODS
This phase 3 trial recruited infants aged 18 to <52 weeks and young children aged 1 to <5 years in The Gambia. Infants randomly assigned to receive one or two doses of one of three lots of nOPV2 or one lot of bivalent OPV (bOPV). Young children were randomised to receive two doses of nOPV2 lot 1 or bOPV. The primary immunogenicity objective was to assess lot-to-lot equivalence of the three nOPV2 lots based on one-dose type 2 poliovirus neutralising antibody seroconversion rates in infants. Equivalence was declared if the 95% CI for the three pairwise rate differences was within the -10% to 10% equivalence margin. Tolerability and safety were assessed based on the rates of solicited adverse events to 7 days, unsolicited adverse events to 28 days, and serious adverse events to 3 months post-dose. Stool poliovirus excretion was examined. The trial was registered as PACTR202010705577776 and is completed.
FINDINGS
Between February and October, 2021, 2345 infants and 600 young children were vaccinated. 2272 (96·9%) were eligible for inclusion in the post-dose one per-protocol population. Seroconversion rates ranged from 48·9% to 49·2% across the three lots. The minimum lower bound of the 95% CIs for the pairwise differences in seroconversion rates between lots was -5·8%. The maximum upper bound was 5·4%. Equivalence was therefore shown. Of those seronegative at baseline, 143 (85·6%) of 167 (95% CI 79·4-90·6) infants and 54 (83·1%) of 65 (71·7-91·2) young children seroconverted over the two-dose nOPV2 schedule. The post-two-dose seroprotection rates, including participants who were both seronegative and seropositive at baseline, were 604 (92·9%) of 650 (95% CI 90·7-94·8) in infants and 276 (95·5%) of 289 (92·4-97·6) in young children. No safety concerns were identified. 7 days post-dose one, 78 (41·7%) of 187 (95% CI 34·6-49·1) infants were excreting the type 2 poliovirus.
INTERPRETATION
nOPV2 was immunogenic and safe in infants and young children in The Gambia. The data support the licensure and WHO prequalification of nOPV2.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Child, Preschool; Humans; Infant; Antibodies, Viral; Antibody Formation; Gambia; Immunization Schedule; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral
PubMed: 38402887
DOI: 10.1016/S0140-6736(23)02844-1 -
Vaccines Feb 2024An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and...
Quantitative Analysis of the Instant and Persistent Inhibition Effects of Maternal Poliovirus Antibodies on the Immune Response in a Phase IV Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.
BACKGROUND
An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet.
OBJECTIVE
In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination.
METHODS
The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer.
RESULTS
The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77-0.82), 0.85 (0.81-0.89), and 0.87 (0.83-0.91) at 30 days after the priming series, 0.86 (0.83-0.89), 0.81 (0.76-0.85), and 0.86 (0.80-0.93) at one year after the priming series, and 0.96 (0.94-0.99), 0.89 (0.86-0.93), and 0.98 (0.93-1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose.
CONCLUSION
A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study's clinical trial registry number is NCT04224519.
PubMed: 38400200
DOI: 10.3390/vaccines12020217 -
Vaccines Jan 2024The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and...
Immune Persistence following Primary Immunization and the Immunogenicity and Safety of a Booster Dose of a Multidose Sabin Strain-Based Inactivated Polio Vaccine in Infants Aged 18 Months.
BACKGROUND
The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months.
METHODS
Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I-III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two.
RESULTS
This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1-3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1-3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively ( = 0.4845).
CONCLUSIONS
The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.
PubMed: 38400106
DOI: 10.3390/vaccines12020123 -
Vaccines Jan 2024Structural and functional commonalities between poliovirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest that poliovirus inoculation may...
BACKGROUND
Structural and functional commonalities between poliovirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggest that poliovirus inoculation may induce antibodies that mitigate the coronavirus disease (COVID-19). No known studies have evaluated COVID-19 risk factors in adults recently vaccinated against poliovirus.
STUDY OBJECTIVE
Among adults with no history of COVID-19 infection or vaccination, who recently received an inactivated poliovirus vaccine (IPV), we sought to determine which biological factors and social determinants of health (SDOH) may be associated with (1) testing positive for SARS-CoV-2, (2) experiencing COVID-19 symptoms, and (3) a longer duration of COVID-19 symptoms.
METHODS
The influence of biological factors and SDOH on SARS-CoV-2 infection and COVID-19 symptoms were evaluated among 282 adults recently inoculated with IPV. Participant-reported surveys were analyzed over 12 months post-enrollment. Bivariate and multivariate linear and logistic regression models identified associations between variables and COVID-19 outcomes.
RESULTS
Adjusting for COVID-19 vaccinations, variants, and other SDOH, secondary analyses revealed that underlying conditions, employment, vitamin D, education, and the oral poliovirus vaccination (OPV) were associated with COVID-19 outcomes. The odds of testing positive for SARS-CoV-2 and experiencing symptoms were significantly reduced among participants who took vitamin D (OR 0.12 and OR 0.09, respectively). Unemployed or part-time working participants were 72% less likely to test positive compared with full-time workers. No prior dose of OPV was one of the strongest predictors of SARS-CoV-2 infection (OR 4.36) and COVID-19 symptoms (OR 6.95).
CONCLUSIONS
Findings suggest that prophylactic measures and mucosal immunity may mitigate the risk and severity of COVID-19 outcomes. Larger-scale studies may inform future policies.
PubMed: 38400105
DOI: 10.3390/vaccines12020121 -
Pathogens (Basel, Switzerland) Jan 2024Upon declaration of poliovirus (PV) type 2 eradication in 2015, the World Health Organization (WHO) published PV containment requirements in the Global Action Plan III...
Upon declaration of poliovirus (PV) type 2 eradication in 2015, the World Health Organization (WHO) published PV containment requirements in the Global Action Plan III (GAPIII) for mitigating the risk of a facility-associated release post eradication. In 2018, the 71st World Health Assembly resolution urged member states retaining PV to appoint a National Authority for Containment (NAC), reduce the number of PV facilities, and submit applications for containment certification. The United States (US) NAC was established in 2018 for containment oversight, and two paths to WHO GAPIII containment certification were developed. Facilities retaining PV were identified through national poliovirus containment surveys. The US NAC conducted 27 site visits at 18 facilities (20 laboratories: A/BSL-2 (65%), A/BSL-3 (20%), and storage-only (15%)) to verify the implementation of US NAC's preliminary containment measures. The NAC identified areas for improvement in seven categories: primary containment, decontamination, hand hygiene, security, emergency response, training, and immunization practices. Sixteen facility applications were endorsed to pursue poliovirus-essential facility (PEF) certification, whereas four facilities opted to withdraw during the containment certification process. The US made noteworthy progress in PV containment to enhance biosafety and biosecurity practices at US PV facilities to safeguard the polio eradication effort.
PubMed: 38392855
DOI: 10.3390/pathogens13020116