Zika and dengue viruses differentially modulate host mRNA processing factors defining its virulence.

Changes in global climate have contributed to increased tick and mosquito (vector) populations and subsequent vector-borne flavivirus infections in humans. This increase poses a threat to the safety of human-derived biologics such as cell and gene therapy. We conducted time-course transcriptomic and protein analyses to uncover host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in relation to host defense mechanisms, as these viruses have caused recent flavivirus outbreaks.

Incidence and window period residual risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in United States blood donations, 2017 to 2023: The transfusion-transmissible infections monitoring system.

Background: The Transfusion-Transmissible Infections Monitoring System assesses trends in ~60% of the US blood supply. Donors with high-risk behaviors, including injection drug use, men having sex with other men, or exchanging sex for money/drugs were deferred for 12 months (12M) from 2016 to 2020 and 3 months (3M) from 2020 to 2023. Here we evaluate HIV, HBV, and HCV incidence and window-period residual risk (WPRR) in two ~3-year periods of 12M (2017-2020) and 3M (2020-2023) to identify any differences.

A review of methodologic & data considerations for vaccine safety surveillance in the wake of the COVID-19 pandemic.

Vaccine safety surveillance systems are vital for the post-market safety monitoring of novel and well-established vaccines, given the sample size, representativeness and follow-up time in clinical trials. The introduction of COVID-19 vaccines during the SARS-CoV-2 pandemic presented unprecedented challenges for safety surveillance. Here, we discuss methodologic considerations for epidemiologic study design and real world data for passive and active surveillance systems for COVID-19 vaccines in the United States (U.

Adopting the estimand framework in prophylactic vaccine trials.

The estimand framework as outlined in ICH E9(R1) has been extensively discussed and implemented in clinical trials of therapeutic products. However, there is limited literature on the application of the framework in preventive vaccine trials, which has many unique characteristics, including emphasis on estimating the per-protocol or "biological" effect. We provide a comprehensive review of the application of the framework to preventive vaccine trials evaluating clinical outcome and immunogenicity, focusing on commonly encountered intercurrent events including but not limited to: noncompliance with vaccination schedule and blood sampling window, infection not meeting protocol definition, death, and use of prohibited products.

NSF is required for diverse endocytic modes by promoting fusion and fission pore closure in secretory cells.

The ATPase N-ethylmaleimide-sensitive factor (NSF), known for disassembling SNARE complexes, plays key roles in neurotransmitter release, neurotransmitter (AMPA, GABA, dopamine) receptor trafficking, and synaptic plasticity, and its dysfunction or mutation is linked to neurological disorders. These roles are largely attributed to SNARE-mediated exocytosis. Here, we reveal a previously unrecognized role for NSF: mediating diverse modes of endocytosis-including slow, fast, ultrafast, overshoot, and bulk-by driving closure of both fusion and fission pores.

A Lyophilizable Nanoparticle Anthrax Vaccine Targeting the Loop-Neutralizing Determinant in Protective Antigen from .

Anthrax remains a formidable bioterrorism threat for which new, optimized and thermostable vaccines are needed. We previously demonstrated that five immunizations of rabbits with a multiple-antigenic-peptide (MAP) vaccine in either Freund's adjuvant or human-use adjuvants can elicit antibody (Ab) against the loop-neutralizing determinant (LND), a cryptic neutralizing epitope in the 2β2-2β3 loop of protective antigen from (), which mediates complete protection of rabbits from inhalation spore challenge with the Ames strain. To develop a more immunogenic vaccine, we molecularly constructed a virus-like particle (VLP) vaccine, comprising the Woodchuck hepatitis core antigen capsid (WHcAg) displaying 240 copies of the LND epitope on each nanoparticle.

Innovative use of self-controlled methods for the evaluation of waning effectiveness of the COVID-19 monovalent third dose: comparison with a test-negative design.

Background: Waning vaccine effectiveness (VE) evaluations are affected by multiple biases, many of which could be implicitly adjusted by using self-controlled methods.

Methods: We used a self-controlled risk interval (SCRI) design to evaluate waning COVID-19 monovalent third dose effectiveness against laboratory-confirmed SARS-CoV-2 medically-attended infections (cases) and hospitalizations with COVID-19 discharge diagnosis among Veterans Health Administration enrollees who received a third dose 15 December 2021-31 August 2022. We used weeks 3-8 post-third dose as reference interval, representing the period of peak VE.

Microfluidic Nanobiosensor Detection of Botulinum Neurotoxin Serotype A.

Botulinum neurotoxin (BoNT) poses a significant threat to public health as the most potent toxin known to humans. BoNT intoxication can lead to botulism, a life-threatening disease that may result from ingesting food contaminated with biologically active BoNT. The gold standard method for BoNT detection, the mouse bioassay, is time-consuming and raises ethical concerns regarding the use of laboratory animals.

Safety monitoring of health outcomes following influenza vaccination during the 2023-2024 season among U.S. Commercially-insured individuals aged 6 months through 64 years: Self-controlled case series analyses.

Background: Influenza vaccines are reformulated annually to target expected virus strains for the upcoming season. Although the safety of seasonal influenza vaccines is well-established, active safety surveillance of reformulated vaccines is essential to assess occurrence of potential health outcomes among vaccinated individuals. This study evaluated the safety of the 2023-2024 influenza vaccines among U.

Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.

Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex-neutralizing antibodies from simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and determine cryo-EM structures for 9. A single V2 apex-neutralizing lineage accounted for cross-clade breadth in most macaques, and somatic hypermutation relative to breadth was generally low, exemplified by antibody V033-a.

-linked glycans on the stalk of influenza virus neuraminidase promote functional tetramer formation by compensating for local hydrophobicity.

Enveloped virus surface antigens, such as influenza neuraminidase (NA), typically depend on linked glycans for assembly, trafficking in the host cell, and immune evasion. Here, we examined the function of the linked glycans on the NA stalk from H1N1 2009 pandemic (pdm09) viruses using reverse genetics coupled with a recombinant NA (rNA) analysis. Our results with the NA from A/Brisbane/02/2018 (H1N1) show that all five glycosylation sites in the stalk generally receive an linked glycan and that viral growth is largely unaffected by removing any of these sites individually.

Analysis of novel zinc-binding proteins in the cell wall of .

Unlabelled: Zinc is a critical nutrient for all living organisms, including bacterial pathogens such as , the causative agent of the severe human respiratory disease diphtheria. As such, zinc acquisition is essential for many pathogens to cause disease. We previously showed that the zinc-regulated ABC transporter encoded by the locus is one of several zinc uptake systems that support the growth of in zinc-limited medium.

The N terminus of H3-influenza hemagglutinin as a site-of-vulnerability to neutralizing antibody.

The N terminus of the H3 subtype of influenza virus hemagglutinin is ∼10 residues longer than the N termini of most other hemagglutinins. As conserved, exposed, and linear regions may be good vaccine targets, we investigated the vaccine utility of the extended H3-N terminus. First, we identified antibody 5E10, for which structure and binding analyses revealed recognition of the H3-N terminus.

Development of a High-throughput Morphological Assay for Evaluating Mesenchymal Stromal Cell-derived Extracellular Vesicle Modulation of Brain Pericyte Secretory Phenotype.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising therapeutic tool for treating many neurodegenerative diseases. Neuroinflammation plays a major role in many of these conditions through an orchestration of interdependent processes that lead to the breakdown of the blood-brain barrier (BBB), infiltration of immune cells and neuronal death. MSC-EVs have shown preliminary evidence of modulating neuroinflammation, but their mechanisms of action are still unknown.

Limb-Girdle Muscular Dystrophy Scientific Workshop: A Multistakeholder Discussion Focused on Charting the Path Forward for Drug Development.

Limb-girdle muscular dystrophy (LGMD) refers to a group of muscular dystrophies that generally result in weakness and loss of limb-girdle muscles, leading to severe disability and early mortality due to cardiac and respiratory complications. Heterogeneity across and within individual LGMD subtypes in addition to variability in progression rates presents significant challenges to traditional drug development approaches for these diseases. In an effort to discuss these challenges, as well as opportunities in support of advancing drug development for LGMD, on February 8, 2024, The Speak Foundation assembled a multistakeholder group consisting of academic medical experts, patients and caregivers, patient advocacy organizations, senior leaders from the US Food and Drug Administration, and commercial drug developers.

Safety monitoring of Pfizer's Respiratory Syncytial Virus Vaccine in pregnant women in the Vaccine Adverse Event Reporting System (VAERS), 2023-2024, United States.

Background: In September 2023, the Advisory Committee on Immunization Practices and the Centers for Disease Control and Prevention (CDC) recommended Pfizer's Respiratory Syncytial Virus (RSV) vaccine for pregnant women at 32-36 weeks' gestation using seasonal administration to prevent RSV-associated lower respiratory tract disease (LRTD) in infants aged <6 months. In clinical trials among pregnant women at 24-36 weeks' gestation, more preterm births and hypertensive disorders of pregnancy were noted among Pfizer's RSV vaccine recipients compared with placebo, but the differences were not statistically significant. Post-licensure safety monitoring of the Pfizer RSV vaccine in pregnant women is important to help inform immunization policies.

CD47-mediated selective accumulation of mature Ly49h+ NK cells to the brain associates with the pathogenesis of cerebral malaria in mice.

CD47 is an antiphagocytic ("don't eat me") signal expressed on all cells that inhibits programmed cell removal of self, and loss of this molecule by aging erythrocytes is associated with increased susceptibility to clearance by macrophages. Previously, we have demonstrated that absence of CD47 confers resistance to infection with nonlethal murine malaria Plasmodium yoelii 17XNL. Furthermore, CD47 blockade with an anti-CD47 monoclonal antibody promotes survival and reduces pathologic features of experimental cerebral malaria (ECM) during infection with lethal murine malaria P.

Antimicrobial Peptides Can Facilitate Whole Blood Safety from Bacteria: A Proof of Concept.

With continuous improvements to blood donor deferrals and the availability of sensitive tests for donation screening for infectious agents, bacterial contamination of whole blood (WB) and blood components stored for transfusion is a rare event. Nonetheless, it still occurs and remains a transfusion-associated risk in terms of septic transfusion reactions (STRs) and transfusion-transmitted bacterial infections with morbidity and mortality outcomes. One of the risk mitigation strategies for bacterial contamination is to implement treatment with currently available proactive pathogen reduction technologies (PRTs) for these transfusion products.

Neutralization Activity of Standard and Hyperimmune Intravenous Immunoglobulins Against Recently Circulating SARS-CoV-2 Variants.

Our study demonstrates that IVIG lots manufactured in 2023-2024 contain neutralizing antibodies against circulating Omicron variants, including KP.3 and XEC. These variants are resistant to all convalescent plasma and IVIG preparations produced prior to 2023.

Summary of taxonomy changes ratified by the International Committee on Taxonomy of Viruses (ICTV) from the Bacterial Viruses Subcommittee, 2025.

This article summarises the activities of the International Committee on Taxonomy of Viruses Bacterial Viruses Subcommittee, detailing developments in the classification of bacterial viruses. We provide here an overview of all new, abolished, moved and renamed taxa proposed in 2024, approved by the Executive Committee, and ratified by membership vote in 2025. Through the collective efforts of 74 international contributors of taxonomy proposals in this round, 43 ratified proposals have led to the creation of one new phylum, one class, four orders, 33 families, 14 subfamilies, 194 genera and 995 species.

Assessing hepatitis B virus infectivity in blood components following pathogen reduction using a human hepatocyte model.

Background: Pathogen reduction technologies (PRTs) have the potential to reduce the risk of emerging transfusion transmissible infections. Evaluating PRT activity against hepatitis B virus (HBV) presents some unique challenges due to the lack of robust model systems. Surrogate viruses (e.

Alteration of Cytokine/Chemokine Transcript Levels in the Placenta of Humanized Mouse Models Treated Prenatally With Dexamethasone.

Background: Dexamethasone (DEX) is used during pregnancies at risk of early delivery or congenital adrenal hyperplasia. DEX exposure is also known to cause placental damage. Although placental cytokines/chemokines protect the fetus and regulate placental development, few studies have examined placental cytokine/chemokine transcript levels in DEX-dosed pregnant mice.

Vaccination with a novel live attenuated strain of Francisella tularensis subsp. tularensis protects cynomolgus macaques against aerosol F. tularensis infection.

Licensed vaccines against Francisella tularensis, a public health threat in some parts of the world and a potential bioterrorism agent, are lacking in Western countries. Existing tularemia vaccine candidates have not been promising in protecting against the most serious respiratory form of tularemia infection. Previous studies identified a novel live attenuated vaccine candidate, F.

SARS-CoV-2 ORF7a activates the endothelium to release von Willebrand factor that promotes thrombosis.

Background: Patients with severe and critical COVID-19 frequently exhibit thromboembolic complications, a significant cause of mortality and morbidity. Increased plasma levels of von Willebrand factor (VWF) following SARS-CoV-2 infection have been extensively reported, which links to thrombosis and increased mortality. However, the mechanism underlying SARS-CoV-2-associated thrombotic complications is not fully understood.

Variation in virulence between three representative pertactin-negative clinical isolates.

Pertussis is a respiratory disease caused by the bacterium . Acellular pertussis (aP) vaccines replaced more reactogenic whole-cell pertussis (wP) vaccines in the United States in the 1990s. Despite high rates of vaccination, a slow but consistent increase in the number of U.