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The Pediatric Infectious Disease Journal Aug 2023This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and Safety of a Hexavalent DTwP-IPV-HB-PRP~T Vaccine Versus Separate DTwP-HB-PRP~T, bOPV, and IPV Vaccines Administered at 2, 4, 6 Months of Age Concomitantly With Rotavirus and Pneumococcal Conjugate Vaccines in Healthy Infants in Thailand.
BACKGROUND
This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine].
METHODS
Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports.
RESULTS
Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group.
CONCLUSIONS
This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines.
Topics: Humans; Infant; Antibodies, Bacterial; Antibodies, Viral; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Hepatitis B; Hepatitis B Vaccines; Immunization Schedule; Poliovirus Vaccine, Inactivated; Rotavirus Vaccines; Thailand; Vaccines, Combined; Vaccines, Conjugate; Pneumococcal Vaccines; Immunogenicity, Vaccine
PubMed: 37257121
DOI: 10.1097/INF.0000000000003975 -
Mathematical Biosciences and... Sep 2023This study presents a novel approach for obtaining reliable models and coefficients to estimate the probability of infection caused by common human enteric viruses. The... (Review)
Review
This study presents a novel approach for obtaining reliable models and coefficients to estimate the probability of infection caused by common human enteric viruses. The aim is to provide guidance for public health policies in disease prevention and control, by reducing uncertainty and management costs in health risk assessments. Conventional dose-response (DR) models, based on the theory elaborated by Furumoto and Mickey , exhibit limitations stemming from the heterogeneity of individual host susceptibilities to infection resulting from ingesting aggregate viruses. Moreover, the scarcity of well-designed viral challenge experiments contributes to significant uncertainty in these DR models. To address these issues, we conducted a review of infection models used in health risk analysis, focusing on (NoV) GI.1, pooled (EV, and via contaminated water or food. Using a mechanistic approach, we reevaluated the known DR models and coefficients for the probability of individual host infection in the mentioned viruses based on dose-infection challenge experiments. Specifically, we sought to establish a relationship between the minimum infectious dose (ID) and the ID having a 50% probability of initiating host infection in the same challenge experiment. Furthermore, we developed a new formula to estimate the degree of aggregation of GI.1 NoV at the mean infectious dose. The proposed models, based on "exact" beta-Poisson DR models, effectively predicted infection probabilities from ingestion of both disaggregated and aggregate NoV GI.1. Through a numerical evaluation, we compared the results with the maximum likelihood estimation (MLE) probability obtained from a controlled challenge trial with the NoV GI.1 virus described in the literature, demonstrating the accuracy of our approach. By addressing the indetermination of the unmeasured degree of NoV aggregation in each single infectious dose, our models reduce overestimations and uncertainties in microbial risk assessments. This improvement enhances the management of health risks associated with enteric virus infections.
Topics: Humans; Enterovirus; Viruses; Norovirus; Water Pollution; Probability
PubMed: 37920063
DOI: 10.3934/mbe.2023777 -
The Journal of Biological Chemistry Nov 2023Positive-strand RNA viruses use long open reading frames to express large polyproteins that are processed into individual proteins by viral proteases. Polyprotein...
Positive-strand RNA viruses use long open reading frames to express large polyproteins that are processed into individual proteins by viral proteases. Polyprotein processing is highly regulated and yields intermediate species with different functions than the fully processed proteins, increasing the biochemical diversity of the compact viral genome while also presenting challenges in that proteins must remain stably folded in multiple contexts. We have used circular dichroism spectroscopy and single molecule microscopy to examine the solution structure and self-association of the poliovirus P3 region protein composed of membrane binding 3A, RNA priming 3B (VPg), 3C protease, and 3D RNA-dependent RNA polymerase proteins. Our data indicate that co-folding interactions within the 3ABC segment stabilize the conformational state of the 3C protease region, and this stabilization requires the full-length 3A and 3B proteins. Enzymatic activity assays show that 3ABC is also an active protease, and it cleaves peptide substrates at rates comparable to 3C. The cleavage of a larger polyprotein substrate is stimulated by the addition of RNA, and 3ABC becomes 20-fold more active than 3C in the presence of stoichiometric amounts of viral cre RNA. The data suggest that co-folding within the 3ABC region results in a protease that can be highly activated toward certain cleavage sites by localization to specific RNA elements within the viral replication center, providing a mechanism for regulating viral polyprotein processing.
Topics: Peptide Hydrolases; Poliovirus; Polyproteins; RNA, Viral; Viral Proteins; Protein Folding; Circular Dichroism; Protein Stability; Enzyme Activation; Protein Structure, Secondary; Amino Acid Sequence
PubMed: 37717698
DOI: 10.1016/j.jbc.2023.105258 -
MBio Nov 2023Multiple pattern recognition receptors sense vRNAs and initiate downstream innate signaling: endosomal Toll-like receptors (TLRs) 3, 7, and 8 and cytoplasmic RIG-I-like...
Multiple pattern recognition receptors sense vRNAs and initiate downstream innate signaling: endosomal Toll-like receptors (TLRs) 3, 7, and 8 and cytoplasmic RIG-I-like receptors (RLRs) RIG-I, and MDA5. They engage distinct signaling scaffolds: mitochondrial antiviral signaling protein (RLR), MyD88, and TLR-adaptor interacting with SLC15A4 on the lysosome (TLR7 and TLR8) and toll/IL-1R domain-containing adaptor inducing IFN (TLR3). By virtue of their unusual vRNA structure and direct host cell entry path, the innate response to EVs uniquely is orchestrated by MDA5. We reported that PVSRIPO's profound attenuation and loss of cytopathogenicity triggers MDA5-directed polar TBK1-IRF3 signaling that generates priming of polyfunctional antitumor CD8 T-cell responses and durable antitumor surveillance . Here we unraveled EV-host relations that control suppression of host type-I IFN responses and show that PVSRIPO's deficient immediate host eIF4G cleavage generates unopposed MDA5-directed downstream signaling cascades resulting in sustained type-I IFN release.
PubMed: 37962360
DOI: 10.1128/mbio.01915-23 -
Emerging Infectious Diseases Aug 2023Guatemala implemented wastewater-based poliovirus surveillance in 2018, and three genetically unrelated vaccine-derived polioviruses (VDPVs) were detected in 2019. The... (Review)
Review
Guatemala implemented wastewater-based poliovirus surveillance in 2018, and three genetically unrelated vaccine-derived polioviruses (VDPVs) were detected in 2019. The Ministry of Health (MoH) response included event investigation through institutional and community retrospective case searches for acute flaccid paralysis (AFP) during 2018-2020 and a bivalent oral polio/measles, mumps, and rubella vaccination campaign in September 2019. This response was reviewed by an international expert team in July 2021. During the campaign, 93% of children 6 months <7 years of age received a polio-containing vaccine dose. No AFP cases were detected in the community search; institutional retrospective searches found 37% of unreported AFP cases in 2018‒2020. No additional VDPV was isolated from wastewater. No evidence of circulating VDPV was found; the 3 isolated VDPVs were classified as ambiguous VDPVs by the international team of experts. These detections highlight risk for poliomyelitis reemergence in countries with low polio vaccine coverage.
Topics: Child; Humans; Poliovirus; Poliovirus Vaccine, Oral; Wastewater; Guatemala; Retrospective Studies; Poliomyelitis; Environmental Monitoring
PubMed: 37486156
DOI: 10.3201/eid2908.230236 -
Neurology(R) Neuroimmunology &... Sep 2023The CD155-CD226/T-cell Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) pathway plays a critical role in regulating T-cell responses and is...
BACKGROUND AND OBJECTIVES
The CD155-CD226/T-cell Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) pathway plays a critical role in regulating T-cell responses and is being targeted clinically. However, research on the role of this pathway in autoimmune diseases is limited. This study aimed to investigate the expression and tissue-specific roles of CD155-CD226/TIGIT pathway molecules in the inflamed muscles of patients with idiopathic inflammatory myopathies (IIMs).
METHODS
Immunohistochemistry, Western blot analysis, and polychromatic immunofluorescence staining were performed to examine the expression of CD155, CD226, and TIGIT in skeletal muscle biopsies from 30 patients with dermatomyositis (DM), 10 patients with amyopathic DM (ADM), 20 patients with immune-mediated necrotizing myopathy (IMNM), 5 patients with dysferlinopathy, and 4 healthy controls. Flow cytometry analysis was used to analyze the functions of T cells with different phenotypes.
RESULTS
Strong expression of CD155 was observed in patients with DM and IMNM, while its expression was largely negative in those with ADM and dysferlinopathy and healthy controls. The costimulatory receptor CD226 was highly expressed on muscle-infiltrating cells, while the coinhibitory receptor TIGIT was expressed at low levels. These infiltrating CD226+ cells were mainly activated effector T cells that localized adjacent to CD155-expressing myofibers, but were faintly detectable within the muscle fascicles lacking CD155. A strong positive correlation between CD155 and CD226 expression scores was also observed. Polychromatic immunofluorescence staining revealed that CD155+ muscle cells coexpressed major histocompatibility complex classes I and II, and tumor necrosis factor alpha expression was detected in CD226+ T cells at their close sites with the myofibers. Furthermore, the expression levels of CD155 and CD226 showed a positive correlation with creatine kinase, lactate dehydrogenase, and the muscle histopathology damage scores and an inverse correlation with the Manual Muscle Testing-8 scores. In addition, CD155 and CD226 expressions were significantly decreased in representative patients who achieved remission posttreatment.
DISCUSSION
These findings demonstrate that the CD155-CD226 axis is highly activated in inflamed muscle tissues of patients with IIM and is associated with muscle disease severity. Our data uncover the immunopathogenic role of the axis in the pathology of IIMs.
Topics: Humans; Inflammation; Muscle, Skeletal; Myositis; Patient Acuity; Receptors, Immunologic; Up-Regulation
PubMed: 37491355
DOI: 10.1212/NXI.0000000000200143 -
The Pan African Medical Journal 2023The Nigeria Polio Emergency Operations Centre (EOC) was established in October 2012 to strengthen coordination, provide strategic direction based on real-time data... (Review)
Review
The Nigeria Polio Emergency Operations Centre (EOC) was established in October 2012 to strengthen coordination, provide strategic direction based on real-time data analysis, and manage all operational aspects of the polio eradication program. The establishment of seven state-level polio EOCs followed. With success achieved in the interruption of wild poliovirus (WPV) transmission as certified in 2020, the future direction of the polio EOC is under consideration. This paper describes the role of the polio EOC in other emergencies and perspectives on future disease control initiatives. A description of the functionality and operations of the polio EOC and a review of documentation of non-polio activities supported by the EOC was done. Key informant insights of national and state-level stakeholders were collected through an electronic questionnaire to determine their perspectives on the polio EOC's contributions and its future role in other public health interventions. The polio EOC structure is based on an incident management system with clear terms of reference and accountability and with full partner coordination. A decline in WPV1 cases was observed from 122 cases in 2012 to 0 in 2015; previously undetected transmission of WPV1 was confirmed in 2016 and all transmission was interrupted under the coordination of the EOCs at national and state levels. During 2014-2019, the polio EOC infrastructure and staff expertise were used to investigate and respond to outbreaks of Ebola, measles, yellow fever, and meningitis and to oversee maternal and neonatal tetanus elimination campaigns. The EOC structure at the national and state levels has contributed to the positive achievements in the polio eradication program in Nigeria and further in the coordination of other disease control and emergency response activities. The transition of the polio EOCs and their capacities to support other non-polio programs will contribute to harnessing the country's capacity for effective coordination of public health initiatives and disease outbreaks.
Topics: Infant, Newborn; Humans; Nigeria; Immunization Programs; Population Surveillance; Poliomyelitis; Poliovirus; Disease Outbreaks; Disease Eradication
PubMed: 38370098
DOI: 10.11604/pamj.supp.2023.45.2.41308 -
The Pan African Medical Journal 2023
Topics: Humans; Nigeria; Poliomyelitis; Global Health; Disease Eradication; Poliovirus Vaccine, Oral; Immunization Programs; Poliovirus
PubMed: 38370100
DOI: 10.11604/pamj.supp.2023.45.2.41049 -
Microorganisms Oct 2023Wastewater surveillance (WWS) was developed in the early 1960s for the detection of poliovirus (PV) circulation in the population. It has been used to monitor several... (Review)
Review
Wastewater surveillance (WWS) was developed in the early 1960s for the detection of poliovirus (PV) circulation in the population. It has been used to monitor several pathogens, including non-polio enteroviruses (NPEVs), which are increasingly recognised as causes of morbidity in children. However, when applying WWS to a new pathogen, it is important to consider the purpose of such a study as well as the suitability of the chosen methodology. With this purpose, the European Non-Polio Enterovirus Network (ENPEN) organised an expert webinar to discuss its history, methods, and applications; its evolution from a culture-based method to molecular detection; and future implementation of next generation sequencing (NGS). The first simulation experiments with PV calculated that a 400 mL sewage sample is sufficient for the detection of viral particles if 1:10,000 people excrete poliovirus in a population of 700,000 people. If the method is applied correctly, several NPEV types are detected. Despite culture-based methods remaining the gold standard for WWS, direct methods followed by molecular-based and sequence-based assays have been developed, not only for enterovirus but for several pathogens. Along with case-based sentinel and/or syndromic surveillance, WWS for NPEV and other pathogens represents an inexpensive, flexible, anonymised, reliable, population-based tool for monitoring outbreaks and the (re)emergence of these virus types/strains within the general population.
PubMed: 37894154
DOI: 10.3390/microorganisms11102496 -
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