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Vaccine Apr 2024This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of adsorbed diphtheria-purified pertussis-tetanus-inactivated polio (Sabin strain)-Haemophilus type b conjugate combined vaccine (DPT-IPV-Hib) in healthy Japanese Infants ≥ 2 and < 43 months of Age: A phase III, multicenter, active controlled, assessor-blinded,...
OBJECTIVE
This study investigated the immunogenicity and safety of a pentavalent vaccine Gobik (DPT-IPV-Haemophilus influenzae type b [Hib]) in healthy Japanese infants aged ≥ 2 and < 43 months using a concomitant vaccination with ActHIB® (Hib) and Tetrabik (DPT-IPV) as a comparator.
METHODS
This study was conducted as a phase 3, multicenter, active controlled, assessor-blinded, randomized, parallel-group study. Participants received a total of 4 subcutaneous doses (3 primary immunization doses and a booster dose) of either the experimental drug (DPT-IPV-Hib) or the active comparator (Hib + DPT-IPV). The primary endpoints were the anti-PRP antibody prevalence rate with ≥ 1 μg/mL, and the antibody prevalence rates against pertussis, diphtheria toxin, tetanus toxin, and attenuated poliovirus after the primary immunization.
RESULTS
In 267 randomized participants (133 in the DPT-IPV-Hib group and 134 in the Hib + DPT-IPV group), the antibody prevalence rates after the primary immunization in both groups were 100.0 % and 88.7 % for anti-PRP antibody with ≥ 1 μg/mL, 99.2 % and 98.5 % against diphtheria toxin, and 100.0 % and 99.2 % against tetanus toxin, respectively. The antibody prevalence rates against pertussis and attenuated poliovirus were 100.0 % in both groups. The non-inferiority of the DPT-IPV-Hib group to the Hib + DPT-IPV group was verified for all measured antibodies. In both groups, all the GMTs of antibodies after the primary immunization were higher than those before the first dose, and those after the booster dose were higher than those after the primary immunization. No safety issues were identified.
CONCLUSION
A single-agent Gobik, the first DPT-IPV-Hib pentavalent vaccine approved in Japan, was confirmed to simultaneously provide primary and booster immunizations against Hib infection, pertussis, diphtheria, tetanus, and poliomyelitis and to have a preventive effect and safety comparable to concomitant vaccination with Hib (ActHIB®) and DPT-IPV quadrivalent vaccine (Tetrabik).
Topics: Infant; Humans; Haemophilus influenzae type b; Japan; Tetanus; Diphtheria; Whooping Cough; Tetanus Toxin; Diphtheria Toxin; Poliovirus Vaccine, Inactivated; Immunization Schedule; Antibodies, Bacterial; Diphtheria-Tetanus-Pertussis Vaccine; Vaccines, Combined; Poliomyelitis; Vaccines, Conjugate; Haemophilus Vaccines
PubMed: 38582691
DOI: 10.1016/j.vaccine.2023.03.077 -
MMWR. Morbidity and Mortality Weekly... Apr 2024The reliable and timely detection of poliovirus cases through surveillance for acute flaccid paralysis (AFP), supplemented by environmental surveillance of sewage...
The reliable and timely detection of poliovirus cases through surveillance for acute flaccid paralysis (AFP), supplemented by environmental surveillance of sewage samples, is a critical component of the polio eradication program. Since 1988, the number of polio cases caused by wild poliovirus (WPV) has declined by >99.9%, and eradication of WPV serotypes 2 and 3 has been certified; only serotype 1 (WPV1) continues to circulate, and transmission remains endemic in Afghanistan and Pakistan. This surveillance update evaluated indicators from AFP surveillance, environmental surveillance for polioviruses, and Global Polio Laboratory Network performance data provided by 28 priority countries for the program during 2022-2023. No WPV1 cases have been detected outside of Afghanistan and Pakistan since August 2022, when an importation into Malawi and Mozambique resulted in an outbreak during 2021-2022. During 2022-2023, among 28 priority countries, 20 (71.4%) met national AFP surveillance indicator targets, and the number of environmental surveillance sites increased. However, low national rates of reported AFP cases in priority countries in 2023 might have resulted from surveillance reporting lags; substantial national and subnational AFP surveillance gaps persist. Maintaining high-quality surveillance is critical to achieving the goal of global polio eradication. Monitoring surveillance indicators is important to identifying gaps and guiding surveillance-strengthening activities, particularly in countries at high risk for poliovirus circulation.
Topics: Humans; alpha-Fetoproteins; Global Health; Population Surveillance; Disease Eradication; Poliomyelitis; Poliovirus; Enterovirus; Immunization Programs
PubMed: 38573841
DOI: 10.15585/mmwr.mm7313a1 -
Global Health, Science and Practice Apr 2024We draw attention to a neglected aspect of poliovirus transmission—the likely role of adults in sustaining transmission—which has important policy and practical...
We draw attention to a neglected aspect of poliovirus transmission—the likely role of adults in sustaining transmission—which has important policy and practical implications for addressing the perplexing phenomenon of continued virus circulation.
Topics: Humans; Poliomyelitis; Infant; Adult; Child; Poliovirus; Child, Preschool
PubMed: 38565256
DOI: 10.9745/GHSP-D-23-00363 -
The Pediatric Infectious Disease Journal Jun 2024
Topics: Poliomyelitis; Humans; Disease Eradication; Global Health; Immunization Programs; Poliovirus Vaccines; Poliovirus Vaccine, Oral
PubMed: 38564755
DOI: 10.1097/INF.0000000000004330 -
Revista Panamericana de Salud Publica =... 2024The Pan American Health Organization (PAHO) and its Member States have been leading the efforts to eradicate wild poliovirus in the Region of Americas since smallpox's...
The Pan American Health Organization (PAHO) and its Member States have been leading the efforts to eradicate wild poliovirus in the Region of Americas since smallpox's successful elimination in 1971. The region became the first to be certified free of wild poliovirus in 1994. However, in July 2022, an unvaccinated patient with no recent travel history was diagnosed with poliomyelitis in the United States of America. In response to the emergence of a circulating vaccine-derived poliovirus in the United States, PAHO established the Polio Incident Management Support Team. This team has been coordinating response efforts, focusing on: coordination, planning, and monitoring; risk communication and community engagement; surveillance and case investigation; vaccination; and rapid response. In this paper, we identified and documented best practices observed following establishment of the Incident Management Support Team (September 2022-2023) through a comprehensive review and analysis of various data sources and country-specific data from the polio surveillance dashboard. The aim was to share these best practices, highlighting technical support and implementation of polio measures by Member States. Despite several challenges, the Americas region remains polio-free. Polio risk is declining, with a July 2023 assessment showing fewer countries at medium, high, and very high risk. This progress reflects improved immunization coverage, surveillance, containment, health determinants, and outbreak preparedness and response. The PAHO Polio Incident Management Support Team has played a key role in supporting these efforts.
PubMed: 38562959
DOI: 10.26633/RPSP.2024.23 -
MedRxiv : the Preprint Server For... Mar 2024Most seasonally circulating enteroviruses result in asymptomatic or mildly symptomatic infections. In rare cases, however, infection with some subtypes can result in...
BACKGROUND
Most seasonally circulating enteroviruses result in asymptomatic or mildly symptomatic infections. In rare cases, however, infection with some subtypes can result in paralysis or death. Of the 300 subtypes known, only poliovirus is reportable, limiting our understanding of the distribution of other enteroviruses that can cause clinical disease.
OBJECTIVE
The overarching objectives of this study were to: 1) describe the distribution of enteroviruses in Arizona during the late summer and fall of 2022, the time of year when they are thought to be most abundant, and 2) demonstrate the utility of viral pan-assay approaches for semi-agnostic discovery that can be followed up by more targeted assays and phylogenomics.
METHODS
This study utilizes pooled nasal samples collected from school-aged children and long-term care facility residents, and wastewater from multiple locations in Arizona during July-October of 2022. We used PCR to amplify and sequence a region common to all enteroviruses, followed by species-level bioinformatic characterization using the QIIME 2 platform. For Enterovirus-D68 (EV-D68), detection was carried out using RT-qPCR, followed by confirmation using near-complete whole EV-D68 genome sequencing using a newly designed tiled amplicon approach.
RESULTS
In the late summer and early fall of 2022, multiple enterovirus species were identified in Arizona wastewater, with Coxsackievirus A6, EV-D68, and Coxsackievirus A19 composing 86% of the characterized reads sequenced. While EV-D68 was not identified in pooled human nasal samples, and the only reported acute flaccid myelitis case in Arizona did not test positive for the virus, an in-depth analysis of EV-D68 in wastewater revealed that the virus was circulating from August through mid-October. A phylogenetic analysis on this relatively limited dataset revealed just a few importations into the state, with a single clade indicating local circulation.
SIGNIFICANCE
This study further supports the utility of wastewater-based epidemiology to identify potential public health threats. Our further investigations into EV-D68 shows how these data might help inform healthcare diagnoses for children presenting with concerning neurological symptoms.
PubMed: 38562876
DOI: 10.1101/2023.11.20.23297677 -
Molecular & Cellular Proteomics : MCP May 2024Picornaviridae represent a large family of single-stranded positive RNA viruses of which different members can infect both humans and animals. These include the...
Picornaviridae represent a large family of single-stranded positive RNA viruses of which different members can infect both humans and animals. These include the enteroviruses (e.g., poliovirus, coxsackievirus, and rhinoviruses) as well as the cardioviruses (e.g., encephalomyocarditis virus). Picornaviruses have evolved to interact with, use, and/or evade cellular host systems to create the optimal environment for replication and spreading. It is known that viruses modify kinase activity during infection, but a proteome-wide overview of the (de)regulation of cellular kinases during picornavirus infection is lacking. To study the kinase activity landscape during picornavirus infection, we here applied dedicated targeted mass spectrometry-based assays covering ∼40% of the human kinome. Our data show that upon infection, kinases of the MAPK pathways become activated (e.g., ERK1/2, RSK1/2, JNK1/2/3, and p38), while kinases involved in regulating the cell cycle (e.g., CDK1/2, GWL, and DYRK3) become inactivated. Additionally, we observed the activation of CHK2, an important kinase involved in the DNA damage response. Using pharmacological kinase inhibitors, we demonstrate that several of these activated kinases are essential for the replication of encephalomyocarditis virus. Altogether, the data provide a quantitative understanding of the regulation of kinome activity induced by picornavirus infection, providing a resource important for developing novel antiviral therapeutic interventions.
Topics: Humans; Picornaviridae; Picornaviridae Infections; HeLa Cells; Proteome; Protein Kinases; Virus Replication; Phosphorylation
PubMed: 38556169
DOI: 10.1016/j.mcpro.2024.100757 -
Cancer Immunology, Immunotherapy : CII Mar 2024Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer...
Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade.
Topics: Humans; Ligands; Killer Cells, Natural; Immunotherapy; Lymphocytes, Tumor-Infiltrating; Neoplasms
PubMed: 38554184
DOI: 10.1007/s00262-024-03671-z -
Pediatrics Jun 2024The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention,...
The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The Advisory Committee on Immunization Practices met February 28 to 29, 2024, to discuss coronavirus disease 2019 vaccines, chikungunya vaccines, diphtheria-tetanus vaccine, influenza vaccines, polio vaccines, respiratory syncytial virus vaccines, meningococcal vaccines, pneumococcal vaccines, and Vaxelis (Diphtheria, Tetanus, Pertussis, Inactivated Poliovirus, Haemophilus influenzae b Conjugate, and Hepatitis B Vaccine). This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information about changes on influenza vaccine composition, meningococcal vaccination considerations, updated guidance for children with a contraindication to pertussis-containing vaccines, and recommendations of the world's first chikungunya vaccine for certain populations.
Topics: Humans; Child; Advisory Committees; COVID-19 Vaccines; Meningococcal Vaccines; United States; Respiratory Syncytial Virus Vaccines; Centers for Disease Control and Prevention, U.S.; COVID-19
PubMed: 38548682
DOI: 10.1542/peds.2024-066653 -
The Journal of Infectious Diseases Mar 2024Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN)...
Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.
PubMed: 38547499
DOI: 10.1093/infdis/jiae154