Safety, tolerability, and efficacy of intranasally-administered detoxified LTh(αK) in mild-to-moderate COVID-19 patients: A randomized, double-blinded, placebo-controlled phase 2 study DOI Creative Commons
Chien‐Yu Cheng,

Ying-Shih Su,

Chyi‐Liang Chen

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2024, Volume and Issue: 20(1)

Published: Nov. 29, 2024

The objective of the study was to assess safety, tolerability, and potential efficacy intranasally administered AD17002, a detoxified form Escherichia coli heat-labile enterotoxin, in treating individuals with mild-to-moderate coronavirus disease 2019 (COVID-19). In this randomized, double-blinded, placebo-controlled phase 2a study, total 30 adults aged 20–70 years COVID-19 were recruited from three medical centers Taiwan 2022–2023. trial comprised two cohorts, participants randomly assigned receive intranasal administrations either doses AD17002 immunomodulator or placebo formulation buffer. Outcome analyses conducted on intention-to-treat set, safety set that included all randomized exposed AD17002. proportion cycle threshold (Ct) ≥30 time recovery key symptoms assessed. An exploratory analyze integrity viral genome after treatment. Administering 20 μg times, at 1-week 1-day intervals, proved be safe well tolerated subjects COVID-19. demonstrated rapid positive outcome reducing load patients receiving Impact treatment further supported by analysis following enhancement clinical within 5 days symptom onset observed but did not achieve statistical significance. According results, administration safe, well-tolerated, potentially effective for

Language: Английский

Accelerated Adaptation of SARS-CoV-2 Variants in Mice Lacking IFITM3 Preserves Distinct Tropism and Pathogenesis DOI Open Access
Parker Denz,

Jonathan L. Papa,

Matthew I. McFadden

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

ABSTRACT Here we investigated whether interferon induced transmembrane protein 3 (IFITM3), a key antiviral deficient in certain human populations, affects interspecies adaptation of SARS-CoV-2. We found that SARS-CoV-2 Beta and Omicron variants passaged through IFITM3-deficient versus wild type mice exhibit enhanced replication pathogenesis this new host species. Enhancements associated with amino acid substitutions the viral genome, suggesting IFITM3 limits accumulation adaptive mutations. Mouse-adapted viruses enabled comparative studies mice. caused lung dysfunction altered cilia-associated gene programs, consistent broad antigen distribution lungs. Omicron, which shows low pathogenicity upper respiratory tract preference humans, replicated to high nasal titers while showing restrained spatial lungs diminished inflammatory responses compared Beta. Our findings demonstrate deficiency accelerates coronavirus reveal intrinsic variant traits shape tropism, immunity, across hosts. HIGHLIGHTS is critical barrier species strains enable pathology favors nose large airways, leading mild exhibits replication, driving severe inflammation

Language: Английский

Citations

1
From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2 DOI Creative Commons
Anoop Kumar, Prajna Tripathi, Prashant Kumar

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 459 - 459

Published: April 25, 2024

Understanding the antibody response to SARS-CoV-2, virus responsible for COVID-19, is crucial comprehending disease progression and significance of vaccine therapeutic development. The emergence highly contagious variants poses a significant challenge humoral immunity, underscoring necessity grasping intricacies specific antibodies. This review emphasizes pivotal role antibodies in shaping immune responses their implications diagnosing, preventing, treating SARS-CoV-2 infection. It delves into kinetics characteristics explores current antibody-based diagnostics, discussing strengths, clinical utility, limitations. Furthermore, we underscore potential SARS-CoV-2-specific antibodies, various therapies such as monoclonal polyclonal anti-cytokines, convalescent plasma, hyperimmunoglobulin-based therapies. Moreover, offer insights vaccines, emphasizing neutralizing order confer immunity along with emerging concern (VOCs) circulating Omicron subvariants. We also highlight challenges field, risks antibody-dependent enhancement (ADE) shed light on associated original antigenic sin (OAS) effect long COVID. Overall, this intends provide valuable insights, which are advancing sensitive diagnostic tools, identifying efficient therapeutics, developing effective vaccines combat evolving threat global scale.

Language: Английский

Citations

5
Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein and potentially drive the genesis of Omicron variants DOI Creative Commons
Qihong Yan, Xijie Gao, Banghui Liu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 31, 2024

Abstract Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population genesis virus has long been suggested but its molecular basis remains poorly understood. Here, we identify a class neutralizing public antibodies defined their shared usage VL6-57 light chains. Although heavy chains diverse genotypes are utilized, convergent HCDR3 rearrangements have observed among these cooperate with germline LCDRs target epitope RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this is present in SARS-CoV-2-naive individuals clonally expanded most COVID-19 patients. We confirm Omicron-specific substitutions at S371, S373 S375 mediate escape the class. These findings support constitutes potential immune pressure promoting introduction S371L/F-S373P-S375F Omicron variants. The results provide further evidence antigenic driven mediated immunity.

Language: Английский

Citations

4
Enhancing Public Health Outcomes with AI-Powered Clinical Surveillance: Precise Detection of COVID-19 Variants using qPCR and Nanopore Sequencing DOI Creative Commons
Hsing‐Yi Chung, Ming‐Jr Jian,

Chih-Kai Chang

et al.

Journal of Infection and Public Health, Journal Year: 2025, Volume and Issue: 18(3), P. 102663 - 102663

Published: Jan. 10, 2025

Language: Английский

Citations

0
Molecular and genetic characteristic of some Omicron variants of the SARS-CoV-2 virus and prospects for vaccine prevention of COVID-19 DOI Creative Commons
В. І. Задорожна, Н. П. Винник, Anton Gerilovych

et al.

One Health Journal, Journal Year: 2025, Volume and Issue: 3(I), P. 5 - 21

Published: Jan. 25, 2025

Over a period of 5 years, the emergent SARS-CoV-2 virus underwent process adaptation to human body as species host and acquired evolutionary changes that bring it closer routine respiratory viruses in terms epidemic clinical characteristics. The work presents systematized information on molecular genetics antigenic characteristics variants virus, categories their potential danger with detailed description spike mutations current sub-variants Omicron (Variants Interest (VOI) - BA.2.86, JN.1; Variants under Monitoring (VUM) JN.1.7, JN.1.18, KP.2, KP.3, KP.3.1.1, LB.1 XEC) its de-escalated subvariants. effect some or combinations properties is characterized. trends prevalence priority VOI VUM world are estimated trend rapid increase intensity circulation KP.3.1.1 XEC against background decrease other fall 2024 shown. issue immune imprinting for COVID-19 associated both natural infection vaccination depending vaccine strain considered. characterization FDA-recommended vaccines 2024/2025 season provided, taking into account manufacturing technology, strains, purpose. Based analysis data effectiveness relation risks infection, severity course disease mortality, need vaccinate individuals only from risk groups, is, according medical age indications, emphasized order reduce mortality. However, composition these must correspond epidemically relevant virus.

Language: Английский

Citations

0
Efficacy of Inactivated Bivalent SARS-CoV-2 Vaccines Targeting Ancestral Strain (ERAGEM), Delta, and Omicron Variants DOI Creative Commons
B. S. Kaplan, Shaikh Terkıs Islam Pavel, Muhammet Ali Uygut

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(2), P. 169 - 169

Published: Feb. 10, 2025

Background/Objectives: The rapid evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the emergence variants with enhanced transmissibility and immune evasion, challenging existing vaccines. This study aimed evaluate immunogenicity protective efficacy inactivated bivalent vaccine formulations incorporating ancestral SARS-CoV-2 strain (ERAGEM) either Delta or Omicron (BA.5) variants. Methods: Bivalent were prepared using beta-propiolactone-inactivated antigens administered K18-hACE2 transgenic mice. Following prime booster immunizations, neutralizing antibody titers viral loads assessed through ELISA, microneutralization assays, quantitative PCR. Mice challenged respective variants, survival rates, temperature, body weight changes monitored for 21 days. Results: Both elicited significant increases in post-booster immunization. ERAGEM + group demonstrated geometric mean (GMTs) 6938.1 4935.0 respectively, while achieved GMTs 16,280.7 24,215.9 Complete (100%) was observed all vaccinated groups post-challenge, no detectable lungs substantial reductions nasal turbinate compared unvaccinated controls. Conclusions: vaccines strong complete protection against disease preclinical models. These findings indicate potential strategies addressing antigenic diversity preparing future pandemics caused by rapidly evolving pathogens.

Language: Английский

Citations

0
Oral Ad5 Vector‐Based SARS‐CoV‐2 Vaccine Effectively Induces Mucosal and Systemic Immune Responses in BALB/c Mice DOI
Tongyao Mao, Xiaozhong Peng, Shibo Jiang

et al.

Journal of Medical Virology, Journal Year: 2025, Volume and Issue: 97(2)

Published: Feb. 1, 2025

ABSTRACT Mucosal immunity is essential for preventing viral infections through the mucosal route. The emerging SARS‐CoV‐2 variants have posed additional hurdles to efficiency of existing vaccines. rapid development novel vaccines that generate broad and systemic could be most effective strategy address this issue. In study, we developed a recombinant replication‐deficient type‐5 adenoviral vaccine with built‐in double‐strand RNA adjuvant expresses Omicron BA.1 spike (S) antigen (hereinafter referred as “the oral vaccine”). We found two doses in BALB/c mice generated long‐lasting S‐specific immune responses, well neutralizing antibodies SIgA antibodies. addition, compared an mRNA booster, using booster induce both immunity, addressing limitation eliciting immunity. Prospective require further investigation into potential applications, particularly challenge experiments, before clinical trials.

Language: Английский

Citations

0
Efficacy and Safety of Acupuncture for Post–COVID-19 Insomnia: Protocol for a Systematic Review and Meta-Analysis DOI Creative Commons
Yadi Li, Jianlong Zhou, Wei Zheng

et al.

JMIR Research Protocols, Journal Year: 2025, Volume and Issue: 14, P. e69417 - e69417

Published: March 3, 2025

The COVID-19 pandemic has had a profound global impact, leading to range of persistent sequelae referred as post-COVID-19 condition or "long COVID" that continue affect patients worldwide. Among these sequelae, insomnia (PCI) emerged significant issue. Conventional treatments, including cognitive behavioral therapy and pharmacological interventions, face limitations such variable efficacy, potential side effects, substantial costs. Recently, acupuncture gained traction due its cost-effectiveness, safety profile. This study aims conduct meta-analysis systematic review evaluating the efficacy for treatment PCI delineate optimal modality, intervention frequency, duration achieving most beneficial outcomes, thereby providing comprehensive understanding acupuncture's role in managing PCI, contributing evidence-based clinical practice, informing decision-making. Electronic searches will be performed 12 databases from inception October 2024 without language restrictions. includes both English (PubMed, Cochrane Library, Web Science, Embase, OVID Scopus), well Chinese (China National Knowledge Infrastructure, Wan-Fang Data, Biomedical Literature Database, Scientific Journal Duxiu Database Clinical Trial Registry Center). Randomized controlled trials on included. Primary outcomes include response rate severity; secondary Traditional Medicine Symptom Scale (TCMSS) adverse event rates. Data synthesis use risk ratios dichotomous data mean differences continuous data. Study selection, extraction, quality assessment conducted independently by 2 reviewers. Methodological eligible studies evaluated following Handbook Systematic Reviews Interventions (version 6.3). Meta-analysis with RevMan 5.3. Based rate, severity, TCMSS score, rates, this provide an treatment. present current evidence aiming inform practices decision-making enhance PCI. Furthermore, it identify research gaps suggest areas future investigation. PROSPERO CRD42024499284; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=499284. DERR1-10.2196/69417.

Language: Английский

Citations

0
Electrochemical pan-variant detection of SARS-CoV-2 through host cell receptor-mimicking molecular recognition DOI
Minjong Lee, Ji‐Soo Kwon, Hong Bin Kim

et al.

Biosensors and Bioelectronics, Journal Year: 2025, Volume and Issue: unknown, P. 117311 - 117311

Published: March 1, 2025

Language: Английский

Citations

0
Design, Synthesis, and Biological Evaluation of Peptidomimetic Tetrahydropyrrole Spirodihydroindolones as SARS-CoV-2 3CL Protease Inhibitors DOI
Lei Hu, Zhihe Zhao, Shujing Zhang

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

The 3CL protease (3CLpro) of SARS-CoV-2 is a key enzyme that plays an essential role in mediating viral replication and transcription. In this study, we synthesized evaluated series peptidomimetic compounds containing tetrahydropyrrole spirodihydroindolone moiety. Among the target compounds, 13c 17d exhibited obvious 3CLpro inhibitory activities with IC50 = 3.71 6.21 nM, respectively. metabolic stability testing liver microsomes, compound showed improved human microsomes. addition, displayed significant anti-SARS-CoV-2 activity high safety Vero E6 cells (EC50 19.26 SI > 400). Further investigations indicated potent against HCoV-OC43 favorable Huh7 61 100). These findings suggest promising lead development novel inhibitors.

Language: Английский

Citations

0