-
Human Vaccines & Immunotherapeutics Dec 2023Poliomyelitis is an acute infectious disease caused by poliovirus. This bibliometric analysis aims to examine the status of poliomyelitis research in the past... (Review)
Review
Poliomyelitis is an acute infectious disease caused by poliovirus. This bibliometric analysis aims to examine the status of poliomyelitis research in the past 20 years. Information regarding polio research was obtained from the Web of Science Core Collection database. CiteSpace, VOSviewer, and Excel were used to perform visual and bibliometric analysis with respect to countries/regions, institutions, authors, journals and keywords. A total of 5,335 publications on poliomyelitis were published from 2002 to 2021. The USA was the county with the majority of publications. Additionally, the most productive institution was the Centers for Disease Control and Prevention. Sutter, RW produced the most papers and had the most co-citations. was the journal with the most polio-related publications and citations. The most common keywords were mainly about polio immunology research ("polio," "immunization," "children," "eradication" and "vaccine"). Our study is helpful for identifying research hotspots and providing direction for future research on poliomyelitis.
Topics: United States; Child; Humans; Poliomyelitis; Bibliometrics; Poliovirus; Centers for Disease Control and Prevention, U.S.; Databases, Factual
PubMed: 36803526
DOI: 10.1080/21645515.2023.2173905 -
Bulletin of the World Health... Dec 2023A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains.
PROBLEM
A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains.
APPROACH
In response to polio outbreaks, the Yemeni health ministry and partners initiated multiple vaccination campaigns to deliver vaccines to children. We also implemented several measures to enhance communication, education, health promotion and hygiene, especially in camps for internally displaced people.
LOCAL SETTING
In 2009, Yemen achieved polio-free status and maintained it until 2019. However, the ongoing political conflict since 2015, coupled with challenges in delivering the polio vaccine to conflict-affected areas, resulted in two polio outbreaks: 35 cases caused by vaccine-derived poliovirus strain 1 between 2019 and 2021, and 230 cases due to vaccine-derived poliovirus strain 2 between November 2021 and December 2022.
RELEVANT CHANGES
In response to the first outbreak, by the end of 2020, we vaccinated 7.2 million children through nationwide vaccination campaigns, except in Sa'ada governorate due to a ban by the authorities. By the end of 2021, 3 800 313 children younger than 5 years had received polio vaccines. For the second outbreak, by the end of 2022, 4 463 389 vaccines had been given to children younger than 10 years, and 1 217 423 to those younger than 5 years.
LESSONS LEARNT
Vaccination campaigns in conflict-affected areas with low vaccine coverage remain crucial in eradicating polio. Efforts are needed to reach vulnerable groups such as displaced populations. Advocacy, communication and social mobilization actions help ensure broader public inclusion and participation in vaccination efforts to prevent polio outbreaks.
Topics: Child; Humans; Yemen; Poliomyelitis; Poliovirus; Poliovirus Vaccines; Disease Outbreaks
PubMed: 38024246
DOI: 10.2471/BLT.23.290122 -
JAMA Oncology Nov 2023Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in...
IMPORTANCE
Inhibition of the T-cell immunoreceptor with Ig and ITIM domains (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of atezolizumab in programmed death ligand 1-selected tumors.
OBJECTIVE
To evaluate the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its combination with atezolizumab in patients with advanced solid tumors.
DESIGN, SETTING, AND PARTICIPANTS
The GO30103 open-label, first-in-human phase 1a/1b dose-escalation and dose-expansion nonrandomized controlled trial was conducted at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 1b. Patients were aged 18 years or older with measurable disease at baseline. The clinical cutoff date was October 1, 2021. Data analysis was performed on January 24, 2022.
INTERVENTIONS
Patients received fixed-dose intravenous tiragolumab on day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients were treated until disease progression, loss of clinical benefit, or development of unacceptable toxicity.
MAIN OUTCOMES AND MEASURES
The primary end points included the safety, tolerability, and recommended phase 2 dose (RP2D) of tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point included the investigator-assessed objective response rate (ORR). Counts and percentages are used for categorical variables, and medians and ranges are used for continuous variables.
RESULTS
Among the phase 1a (n = 24) and 1b (n = 49) dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 25-81) years, respectively. More than half of patients were women (14 of 24 [58%] and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 or more prior cancer therapies. No dose-limiting toxicities occurred, and the maximum tolerated dose of tiragolumab was not reached (NR). The most frequent treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor activity in 6% of patients (n = 3) during phase 1b. The safety profile of combination tiragolumab plus atezolizumab in phase 1b was similar in the dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) in the non-small cell lung cancer (NSCLC) cohort (median duration of response [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 15.2 [95% CI, 7.0 to NR] months).
CONCLUSIONS AND RELEVANCE
In this nonrandomized controlled trial, tiragolumab was well tolerated with or without atezolizumab; no new safety signals were observed. Preliminary antitumor activity was demonstrated for the combination regimen in patients with cancer immunotherapy-naive metastatic NSCLC or EC.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02794571.
Topics: Humans; Female; Middle Aged; Male; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antineoplastic Agents; Esophageal Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Receptors, Immunologic
PubMed: 37768658
DOI: 10.1001/jamaoncol.2023.3867 -
Nucleic Acids Research Sep 2023The genomes of positive-strand RNA viruses serve as a template for both protein translation and genome replication. In enteroviruses, a cloverleaf RNA structure at the...
The genomes of positive-strand RNA viruses serve as a template for both protein translation and genome replication. In enteroviruses, a cloverleaf RNA structure at the 5' end of the genome functions as a switch to transition from viral translation to replication by interacting with host poly(C)-binding protein 2 (PCBP2) and the viral 3CDpro protein. We determined the structures of cloverleaf RNA from coxsackievirus and poliovirus. Cloverleaf RNA folds into an H-type four-way junction and is stabilized by a unique adenosine-cytidine-uridine (A•C-U) base triple involving the conserved pyrimidine mismatch region. The two PCBP2 binding sites are spatially proximal and are located on the opposite end from the 3CDpro binding site on cloverleaf. We determined that the A•C-U base triple restricts the flexibility of the cloverleaf stem-loops resulting in partial occlusion of the PCBP2 binding site, and elimination of the A•C-U base triple increases the binding affinity of PCBP2 to the cloverleaf RNA. Based on the cloverleaf structures and biophysical assays, we propose a new mechanistic model by which enteroviruses use the cloverleaf structure as a molecular switch to transition from viral protein translation to genome replication.
Topics: Humans; Enterovirus; Genome, Viral; HeLa Cells; Nucleic Acid Conformation; Poliovirus; Protein Biosynthesis; RNA, Viral; RNA-Binding Proteins; Viral Proteins; Virus Replication
PubMed: 37486760
DOI: 10.1093/nar/gkad618 -
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 -
International Journal of Molecular... Nov 2023Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide.... (Review)
Review
Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide. Kaempferol and its compounds have well-known antioxidant, anti-inflammatory and antimicrobial properties among other health benefits. However, the antiviral properties of kaempferol are notable, and there is a significant number of experimental studies on this topic. Kaempferol compounds were effective against DNA viruses such as hepatitis B virus, viruses of the alphaherpesvirinae family, African swine fever virus, and pseudorabies virus; they were also effective against RNA viruses, namely feline SARS coronavirus, dengue fever virus, Japanese encephalitis virus, influenza virus, enterovirus 71, poliovirus, respiratory syncytial virus, human immunodeficiency virus, calicivirus, and chikungunya virus. On the other hand, no effectiveness against murine norovirus and hepatitis A virus could be determined. The antiviral action mechanisms of kaempferol compounds are various, such as the inhibition of viral polymerases and of viral attachment and entry into host cells. Future research should be focused on further elucidating the antiviral properties of kaempferol compounds from different plants and assessing their potential use to complement the action of antiviral drugs.
Topics: Swine; Animals; Cats; Humans; Mice; Kaempferols; African Swine Fever Virus; RNA Viruses; Enterovirus; Antiviral Agents
PubMed: 38003488
DOI: 10.3390/ijms242216299