An Old Acquaintance: Could Adenoviruses Be Our Next Pandemic Threat?

Viruses, Год журнала: 2023, Номер 15(2), С. 330 - 330

Опубликована: Янв. 24, 2023

Human adenoviruses (HAdV) are one of the most important pathogens detected in acute respiratory diseases pediatrics and immunocompromised patients. In 1953, Wallace Rowe described it for first time oropharyngeal lymphatic tissue. To date, more than 110 types HAdV have been described, with different cellular tropisms. They can cause gastrointestinal symptoms, even urinary tract inflammation, although infections asymptomatic. However, there is a population at risk that develop serious lethal conditions. These viruses double-stranded DNA genome, 25–48 kbp, 90 nm diameter, without mantle, stable environment, resistant to fat-soluble detergents. Currently diagnosis made lateral flow immunochromatography or molecular biology through polymerase chain reaction. This review aimed highlight variability pandemic potential HAdV3 7 recombinant could considering aggressive outbreaks produced health facilities. Herein, we characteristics HAdV, from infection treatment, vaccine development, evaluation social determinants associated suggesting necessary measures future sanitary control prevent disasters such as SARS-CoV-2 pandemic, an emphasis on use AdV vaccines other pandemics.

Язык: Английский

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Impact of COVID-19 on antibiotic usage in primary care: a retrospective analysis

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Фев. 27, 2024

Abstract The COVID-19 pandemic has contributed to many changes in the medical practice, including a wider access tele-consultations. It not only influenced type of treatment but also shed light on mistakes often made by doctors, such as abuse antibiotics. This study aimed evaluate antibiotic treatment, and impact prescribing during GP’s visit. retrospective history analysis involved data from first-contact center (Pantamed, Olsztyn, Poland), 1 January 2018 31 May 2023. Quantities prescribed antibiotics were assessed converted into so-called active list for given working day adult patients (> 18 years age). Statistical based collective was performed. During pandemic, decline number consultations been observed, both remotely via tele-medicine personal appointments, compared before pandemic: n = 95,251 versus 79,619. Also, there decrease total amount relative (2.44 vs. 4.54; p > 0.001). quantities did depend way doctor provided. changing family doctors’ management respiratory infections. ability identify etiological agent—the SARS-COV2 virus—contributed reduction use.

Язык: Английский

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Genomic similarity and antibody-dependent enhancement of immune serum potentially affect the protective efficacy of commercial MLV vaccines against NADC30-like PRRSV

Virologica Sinica, Год журнала: 2023, Номер 38(5), С. 813 - 826

Опубликована: Сен. 1, 2023

Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant diseases affecting pig industry worldwide. The PRRSV mutation rate highest among RNA viruses. To date, NADC30-like highly pathogenic (HP-PRRSV) are dominant epidemic strains in China; however, commercial vaccines do not always provide sufficient cross-protection, reasons for insufficient protection unclear. This study isolated a wild-type PRRSV, SX-YL1806, from Shaanxi Province. Vaccination challenge experiments piglets showed that modified live virus (MLV) provided good against HP-PRRSV. However, it could novel strain SX-YL1806. explore this phenomenon, we compared genomic homology between MLV HP-PRRSV or found had lower genome similarity with PRRSV. Serum neutralization assay MLV-immune serum slightly promoted homologous replication significantly heterologous vitro, suggesting antibody-dependent enhancement (ADE) might also play role decreasing protective efficacy. These findings expand our understanding potential factors effect strains.

Язык: Английский

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Suramin inhibits SARS-CoV-2 nucleocapsid phosphoprotein genome packaging function

Virus Research, Год журнала: 2023, Номер 336, С. 199221 - 199221

Опубликована: Сен. 15, 2023

The coronavirus disease 2019 (COVID-19) pandemic is fading, however its etiologic agent severe acute respiratory syndrome 2 (SARS-CoV-2) continues posing - despite the availability of licensed vaccines a global health threat, due to potential emergence vaccine-resistant SARS-CoV-2 variants. This makes development new drugs against COVID-19 persistent urgency and sets as research priority validation novel therapeutic targets within proteome. Among these, promising one nucleocapsid (N) phosphoprotein, major structural component virion with indispensable role in packaging viral genome into ribonucleoprotein (RNP) complex, which also contributes innate immune evasion by inhibiting host cell type-I interferon (IFN-I) response. By combining miniaturized differential scanning fluorimetry microscale thermophoresis, we found that 100-year-old drug Suramin interacts N-terminal domain (NTD) C-terminal (CTD), thereby their single-stranded RNA (ssRNA) binding function low-micromolar Kd IC50 values. Molecular docking suggests basic NTD cleft CTD dimer interface groove, highlighting three potentially druggable ssRNA sites. Electron microscopy shows inhibits formation vitro RNP complex-like condensates N synthetic ssRNA. In dose-dependent manner, reduced SARS-CoV-2-induced cytopathic effect on Vero E6 Calu-3 cells, partially reverting N-inhibited IFN-I production 293T cells. Our findings indicate replication hampering packaging, representing starting model for design antivirals.

Язык: Английский

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Enhancing Individual UAV Path Planning With Parallel Multi-Swarm Treatment Coronavirus Herd Immunity Optimizer (PMST-CHIO) Algorithm

IEEE Access, Год журнала: 2024, Номер 12, С. 28395 - 28416

Опубликована: Янв. 1, 2024

This paper introduces the PMST-CHIO, a novel variant of Coronavirus Herd Immunity Optimizer (CHIO) algorithm, exclusively tailored for individual unmanned aerial vehicle (UAV) path planning in complex 3D environments. While acknowledging and building upon foundational principles derived from UAV swarm research, PMST-CHIO distinctively focuses on optimizing trajectory single UAVs. It innovatively integrates parallel multi-swarm treatment mechanism, enhancing standard CHIO's exploration exploitation capabilities significantly. mechanism diverges swarm-based approaches by deploying multiple instances CHIO optimizer, each functioning autonomously within its sub-swarm, thereby facilitating independent These or candidates, operate concert to determine optimal collision-free routes, taking into account unique characteristics UAVs intricacies service area. The algorithm incorporates two key mechanisms: 1) global exploitation, employing best solution identified highest performing candidate across swarms; 2) strategic shift focused top-performing after specific iteration threshold is reached. adaptation significantly improves algorithm's search efficiency, convergence behavior, navigational accuracy under challenging Extensive simulations comparative studies validate that can effectively overcome limitations yielding safer, shorter, more compliant flight paths intricate landscapes.

Язык: Английский

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The Ambivalence of Post COVID-19 Vaccination Responses in Humans

Biomolecules, Год журнала: 2024, Номер 14(10), С. 1320 - 1320

Опубликована: Окт. 17, 2024

The Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has prompted a massive global vaccination campaign, leading to the rapid development and deployment of several vaccines. Various COVID-19 vaccines are under different phases clinical trials include whole virus or its parts like DNA, mRNA, protein subunits administered directly through vectors. Beginning in 2020, few mRNA (Pfizer-BioNTech BNT162b2 Moderna mRNA-1273) adenovirus-based (AstraZeneca ChAdOx1-S Janssen Ad26.COV2.S) were recommended WHO for emergency use before completion phase 3 4 trials. These mostly two three doses at defined frequency between doses. While these vaccines, mainly based on viral nucleic acids conferred protection against progression SARS-CoV-2 infection into COVID-19, prevented death due disease, their also been accompanied plethora side effects. Common effects localized reactions such as pain injection site, well systemic fever, fatigue, headache. symptoms generally mild moderate resolve within days. However, rare but more serious have reported, including allergic anaphylaxis and, some cases, myocarditis pericarditis, particularly younger males. Ongoing surveillance research efforts continue refine understanding adverse effects, providing critical insights risk-benefit profile Nonetheless, overall safety supports continued combating with regulatory agencies health organizations emphasizing importance preventing COVID-19's outcomes. In this review, we describe types summarize various autoimmune inflammatory response(s) manifesting predominantly cardiac, hematological, neurological, psychological dysfunctions. incidence, presentation, risk factors, diagnosis, management possible mechanisms contributing discussed. review highlights potential ambivalence human response post-COVID-19 necessitates need mitigate

Язык: Английский

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Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial

Vaccines, Год журнала: 2023, Номер 11(2), С. 455 - 455

Опубликована: Фев. 16, 2023

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted randomized, double-blind, placebo-controlled, phase I trial. Three strengths were compared with an adjuvant-only preparation. It included two intramuscular third intranasal dose. Eligible participants followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, cell-mediated immunity assessed. Results: A total 153 enrolled (13 sentinels, 120 20 non-randomized open-labeled IgA assessment). No related serious event was observed. The geometric mean ratios (GMRs) 95% CI serum antibodies placebo weeks after second injection 5.82 (1.46–23.13), 11.12 (2.74–45.09), 20.70 (5.05–84.76) in 5, 10, µg groups, respectively. GMR anti-RBD mucosal fluid dose 23.27 (21.27–25.45) 10 group. humoral responses sustained up five months. All indicated strong T-helper 1 response. Conclusion: RCP is safe creates durable cellular good immune response its /200 µL strengths. Trial registration: IRCT20201214049709N1.

Язык: Английский

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A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 20, 2023

Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) currently in clinical development. Published evidence has demonstrated can induction neutralizing antibodies SARS-CoV-2 humans and animal models. However, characteristics mechanisms immune responses induced by not yet known. To characterize A-910823, we compared adaptive response profile enhanced with other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, empty lipid nanoparticle [eLNP]) murine model. Compared humoral to an equal greater extent following potent T follicular helper (Tfh) germinal center B (GCB) cell induction, without inducing strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing produced similar results even when given as booster dose primary administration nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation modified identify which components play role driving effect detailed evaluation immunological each showed immunity Tfh GCB were dependent on α-tocopherol. Finally, revealed recruitment cells draining lymph nodes serum cytokines chemokines also α-tocopherol component. This study demonstrates capable robust responses, dose. The findings emphasize drives Tfh-inducing function A-910823. Overall, our data provide key information may inform future production improved adjuvants.

Язык: Английский

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DS-5670a, a novel mRNA-encapsulated lipid nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2: Results from a phase 2 clinical study

Vaccine, Год журнала: 2023, Номер 41(38), С. 5525 - 5534

Опубликована: Авг. 1, 2023

DS-5670a is a vaccine candidate for coronavirus disease 2019 (COVID-19) harnessing novel modality composed of messenger ribonucleic acid (mRNA) encoding the receptor-binding domain (RBD) from spike protein severe acute respiratory syndrome 2 (SARS-CoV-2) encapsulated in lipid nanoparticles. Here, we report safety, immunogenicity, and pharmacokinetic profile phase clinical trial healthy adults who were immunologically naïve to SARS-CoV-2.The study consisted an open-label, uncontrolled, dose-escalation part double-blind, randomized, 2-arm, parallel-group part. A total 80 Japanese participants assigned receive intramuscular DS-5670a, containing either 30 or 60 µg mRNA, as two injections administered 4 weeks apart. Safety was assessed by characterization treatment-emergent adverse events (TEAEs). Immunogenicity neutralization titers against SARS-CoV-2, anti-RBD immunoglobulin (Ig)G levels, SARS-CoV-2 spike-specific T cell responses. Plasma parameters also evaluated.Most solicited TEAEs mild moderate with both mRNA doses. Four (10 %) group developed redness at injection site, but all cases resolved without treatment. There no serious leading discontinuation. Humoral immune responses dose groups greater than those observed human convalescent serum; produced better Neutralization found be correlated IgG levels (specifically IgG1). elicited antigen-specific helper 1-polarized cellular responses.The mRNA-based provided favorable clinically acceptable safety profile. Confirmatory trials are currently ongoing evaluate immunogenicity primary assess when heterologous homologous booster.https://jrct.niph.go.jp/latest-detail/jRCT2071210086.

Язык: Английский

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Indirect Dispersion of SARS-CoV-2 Live-Attenuated Vaccine and Its Contribution to Herd Immunity

Vaccines, Год журнала: 2023, Номер 11(3), С. 655 - 655

Опубликована: Март 14, 2023

It has been 34 months since the beginning of SARS-CoV-2 coronavirus pandemic, which causes COVID-19 disease. In several countries, immunization reached a proportion near what is required to reach herd immunity. Nevertheless, infections and re-infections have observed even in vaccinated persons. That because protection conferred by vaccines not entirely effective against new virus variants. unknown how often booster will be necessary maintain good level protective Furthermore, many individuals refuse vaccination, developing large population yet vaccinated. Some live-attenuated are being developed. Here, we analyze indirect dispersion from their contacts contribution that this phenomenon could reaching Herd Immunity.

Язык: Английский

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