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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 -
Automated detection and classification of polioviruses from nanopore sequencing reads using piranha.Virus Evolution 2024Widespread surveillance, rapid detection, and appropriate intervention will be critical for successful eradication of poliovirus. Using deployable next-generation...
Widespread surveillance, rapid detection, and appropriate intervention will be critical for successful eradication of poliovirus. Using deployable next-generation sequencing (NGS) approaches, such as Oxford Nanopore Technologies' MinION, the time from sample to result can be significantly reduced compared to cell culture and Sanger sequencing. We developed piranha (poliovirus investigation resource automating nanopore haplotype analysis), a 'sequencing reads-to-report' solution to aid routine poliovirus testing of both stool and environmental samples and alleviate the bioinformatic bottleneck that often exists for laboratories adopting novel NGS approaches. Piranha can be used for efficient intratypic differentiation of poliovirus serotypes, for classification of Sabin-like polioviruses, and for detection of wild-type and vaccine-derived polioviruses. It produces interactive, distributable reports, as well as summary comma-separated values files and consensus poliovirus FASTA sequences. Piranha optionally provides phylogenetic analysis, with the ability to incorporate a local database, processing from raw sequencing reads to an interactive, annotated phylogeny in a single step. The reports describe each nanopore sequencing run with interpretable plots, enabling researchers to easily detect the presence of poliovirus in samples and quickly disseminate their results. Poliovirus eradication efforts are hindered by the lack of real-time detection and reporting, and piranha can be used to complement direct detection sequencing approaches.
PubMed: 38544854
DOI: 10.1093/ve/veae023 -
Vaccines Feb 2024Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks....
Poliovirus-Neutralizing Antibody Seroprevalence and Vaccine Habits in a Vaccine-Derived Poliovirus Outbreak Region in the Democratic Republic of Congo in 2018: The Impact on the Global Eradication Initiative.
Despite the successes in wild-type polio eradication, poor vaccine coverage in the DRC has led to the occurrence of circulating vaccine-derived poliovirus outbreaks. This cross-sectional population-based survey provides an update to previous poliovirus-neutralizing antibody seroprevalence studies in the DRC and quantifies risk factors for under-immunization and parental knowledge that guide vaccine decision making. Among the 964 children between 6 and 35 months in our survey, 43.8% (95% CI: 40.6-47.0%), 41.1% (38.0-44.2%), and 38.0% (34.9-41.0%) had protective neutralizing titers to polio types 1, 2, and 3, respectively. We found that 60.7% of parents reported knowing about polio, yet 25.6% reported knowing how it spreads. Our data supported the conclusion that polio outreach efforts were successfully connecting with communities-79.4% of participants had someone come to their home with information about polio, and 88.5% had heard of a polio vaccination campaign. Additionally, the odds of seroreactivity to only serotype 2 were far greater in health zones that had a history of supplementary immunization activities (SIAs) compared to health zones that did not. While SIAs may be reaching under-vaccinated communities as a whole, these results are a continuation of the downward trend of seroprevalence rates in this region.
PubMed: 38543880
DOI: 10.3390/vaccines12030246 -
Vaccines Feb 2024Prior research explores whether seasonal and childhood vaccines mitigate the risk of SARS-CoV-2 infection. Although there are trials investigating COVID-19 infection in...
Prior research explores whether seasonal and childhood vaccines mitigate the risk of SARS-CoV-2 infection. Although there are trials investigating COVID-19 infection in response to the effects of the oral poliovirus vaccine (OPV), there has been no prior research assessing COVID-19 outcomes in recently immunized adults with the inactivated poliovirus vaccine (IPV). SARS-CoV-2 infection and COVID-19 symptoms were analyzed across a cohort of 282 adults who received an IPV booster. Bivariate and multivariate regression models explored associations among variables related to vaccination histories and COVID-19 outcomes. One year post-IPV inoculation, participants who had never received OPV were more likely to test positive for SARS-CoV-2 and experience COVID-19 symptoms, compared to those who had previously received OPV (OR = 3.92, 95%CI 2.22-7.03, < 0.001; OR = 4.45, 95%CI 2.48-8.17, < 0.001, respectively). Those who had never received OPV experienced COVID-19 symptoms for 6.17 days longer than participants who had previously received OPV (95%CI 3.68-8.67, < 0.001). Multivariate regression modeling indicated COVID-19 vaccination did not impact SARS-CoV-2 infection or COVID-19 symptoms in this sample of adults who had recently received IPV. Findings suggest IPV may boost mucosal immunity among OPV-primed individuals, and COVID-19 vaccination may not provide additional protection among those who had received IPV. Future, larger-scale studies should measure the extent of protective effects against COVID-19 to inform public health policies in resource-deficient settings.
PubMed: 38543853
DOI: 10.3390/vaccines12030219 -
Pathogens (Basel, Switzerland) Mar 2024Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to... (Review)
Review
Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities.
PubMed: 38535567
DOI: 10.3390/pathogens13030224 -
Pathogens (Basel, Switzerland) Feb 2024Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due...
Polio-associated paralysis is one of the diseases under national surveillance in the Democratic Republic of the Congo (DRC). Although it has become relatively rare due to control measures, non-polio paralysis cases are still reported and constitute a real problem, especially for etiological diagnosis, which is necessary for better management and response. From September 2022 to April 2023, we investigated acute flaccid paralysis (AFP) cases in Kinshasa following an alert from the Provincial Division of Health. All suspected cases and their close contacts were investigated and sampled. Among the 57 sampled patients, 21 (36.8%) were suspects, and 36 (63.2%) were contacts. We performed several etiological tests available in the laboratory, targeting viruses, including Poliovirus, Influenza virus, SARS-CoV-2, Enterovirus, and arboviruses. No virus material was detected, but the serological test (ELISA) detected antibodies against Chikungunya Virus, i.e., 47.4% (27/57) for IgM and 22.8% (13/57) for IgG. Among suspected cases, we detected 33.3% (7/21) with anti-Chikungunya IgM and 14.3% (3/21) of anti-Chikungunya IgG. These results highlight the importance of enhancing the epidemiological surveillance of Chikungunya.
PubMed: 38535541
DOI: 10.3390/pathogens13030198 -
Pathogens (Basel, Switzerland) Feb 2024Pakistan is one of two countries globally still endemic for poliovirus. While increasing immunization coverage is a concern, providing equitable access to care is also a...
Pakistan is one of two countries globally still endemic for poliovirus. While increasing immunization coverage is a concern, providing equitable access to care is also a priority, especially for conflict-affected populations. Recognizing these challenges, , an integrated model of maternal, newborn, and child health (MNCH), immunization, and nutrition services delivered through community mobilization, mobile outreach, and private-sector engagement was implemented in conflict-affected union councils (UCs) with high poliovirus transmission, including Kharotabad 1(Quetta, Balochistan) and Bakhmal Ahmedzai (Lakki Marwat, Khyber Pakhtunkhwa). A quasi-experimental pre-post-design was used to assess the impact of the interventions implemented between April 2021 and April 2022, with a baseline and an endline survey. For each of the intervention UCs, a separate, matched-control UC was identified. At endline, the proportion of fully immunized children increased significantly from 27.5% to 51.0% in intervention UCs with a difference-in-difference (DiD) estimate of 13.6%. The proportion of zero-dose children and non-recipients of routine immunization (NR-RI) children decreased from 31.6% to 0.9% and from 31.9% to 3.4%, respectively, with a significant decrease in the latter group. Scaling up and assessing the adoption and feasibility of integrated interventions to improve immunization coverage can inform policymakers of the viability of such services in such contexts.
PubMed: 38535529
DOI: 10.3390/pathogens13030185 -
Pathogens (Basel, Switzerland) Feb 2024The Global Polio Eradication Initiative made immense progress after its establishment in 1988 as a consequence of high coverage with various poliovirus vaccines in all... (Review)
Review
The Global Polio Eradication Initiative made immense progress after its establishment in 1988 as a consequence of high coverage with various poliovirus vaccines in all populations of the world. Problems have arisen in recent years, however, related to security issues in some countries, to the circulation of vaccine-derived polioviruses, and to the recognition that individuals with certain immune deficiencies can remain infected and infectious for many months or years. As natural infection and different vaccines have different effects on the immune system, the patterns of humoral and mucosal immunity to polioviruses in the world today are complex but are crucial to the ultimate success of the eradication initiative. This paper describes the background of the current situation and current immunological patterns and discusses their implications for managing population immunity to polioviruses in the years ahead.
PubMed: 38535527
DOI: 10.3390/pathogens13030183