We performed a systems vaccinology analysis to investigate immune responses in humans to an H5N1 influenza vaccine, with and without the AS03 adjuvant, to identify factors influencing antibody response magnitude and durability. Our findings revealed a platelet and adhesion-related blood transcriptional signature on day 7 that predicted the longevity of the antibody response, suggesting a potential role for platelets in modulating antibody response durability. As platelets originate from megakaryocytes, we explored the effect of thrombopoietin (TPO)-mediated megakaryocyte activation on antibody response longevity.
View Article and Find Full Text PDFThis study showed that a severe acute respiratory syndrome coronavirus 2 infection reduced the risk of reinfection among vaccinated individuals by 0.50 (95% CI, 0.39-0.
View Article and Find Full Text PDFNipah virus causes highly lethal disease, with case-fatality rates ranging from 40% to 100% in recognised outbreaks. No treatments or licensed vaccines are currently available for the prevention and control of Nipah virus infection. In 2019, WHO published an advanced draft of a research and development roadmap for accelerating development of medical countermeasures, including diagnostics, therapeutics, and vaccines, to enable effective and timely emergency response to Nipah virus outbreaks.
View Article and Find Full Text PDFRuthenium complexes containing triphenylphosphine diamide ligands were prepared, characterized, and tested for their biological activity against various cancer cell lines and the malaria parasite, Plasmodium falciparum. The effect of M (mono-substituted) and B (bis-substituted) complexes on the human cervical carcinoma (HeLa) cell line was investigated using the MTT assay. Five (B2, B3, B5, B6, and B13) of the 24 synthesized ruthenium complexes showed significant effects with IC values ranging between 0.
View Article and Find Full Text PDFBackground: When studying the development of children through the preteen years into adolescence, it is often important to link features of their physical and mental health to the stage of puberty at the time. This is complex since individuals vary substantially in the ages at which they reach different pubertal milestones.
Methods: The Avon Longitudinal Study of Parents and Children (ALSPAC) is an ongoing longitudinal cohort study based in southwest England that recruited over 14000 women in pregnancy, with expected dates of delivery between April 1991 and December 1992.
Reverse zoonotic transmission events of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been described since the start of the pandemic, and the World Organisation for Animal Health (WOAH) designated the detection of SARS-CoV-2 in animals a reportable disease. Eighteen domestic and zoo animals in Great Britain and Jersey were tested by APHA for SARS-CoV-2 during 2020-2023. One domestic cat (), three domestic dogs (), and three Amur tigers () from a zoo were confirmed positive during 2020-2021 and reported to the WOAH.
View Article and Find Full Text PDFViolence Against Women
April 2024
This study investigated how jurors use deoxyribonucleic acid (DNA) evidence in an adult rape trial with a female victim and a male stranger defendant. Community members read a trial summary and then made case judgments (e.g.
View Article and Find Full Text PDFRecombinant Factor VIII-Fc fusion protein (rFVIIIFc) is an enhanced half-life therapeutic protein product used for the management of hemophilia A. Recent studies have demonstrated that rFVIIIFc interacts with Fc gamma receptors (FcγR) resulting in the activation or inhibition of various FcγR-expressing immune cells. We previously demonstrated that rFVIIIFc, unlike recombinant Factor IX-Fc (rFIXFc), activates natural killer (NK) cells via Fc-mediated interactions with FcγRIIIA (CD16).
View Article and Find Full Text PDFBackground: The recent discovery of emerging relapsing fever group Borrelia (RFGB) species, such as Borrelia miyamotoi, poses a growing threat to public health. However, the global distribution and associated risk burden of these species remain uncertain. We aimed to map the diversity, distribution, and potential infection risk of RFGB.
View Article and Find Full Text PDFDetecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfections is challenging with current serology assays and is further complicated by the marked decrease in routine viral testing practices as viral transmission increased during Omicron. Here, we provide proof-of-principle that high-avidity anti-nucleocapsid (N) antibodies detects reinfections after a single infection with higher specificity (85%; 95% confidence interval [95% CI], 80%-90%) compared to anti-N antibody levels (72%; 95% CI, 66%-79%) in a vaccinated cohort. This method could be used to retroactively investigate the epidemiology and incremental long-term health consequences of SARS-CoV-2 reinfections.
View Article and Find Full Text PDFWe conducted an analysis to better understand the potential factors impacting host adaptation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in white-tailed deer, humans, and mink due to the strong evidence of sustained transmission within these hosts. Classification models trained on single nucleotide and amino acid differences between samples effectively identified white-tailed deer-, human-, and mink-derived SARS-CoV-2. For example, the balanced accuracy score of Extremely Randomized Trees classifiers was 0.
View Article and Find Full Text PDFImmunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike elicits neutralizing antibodies (nAbs) against difficult-to-neutralize variants of concern (VOCs) remains an area of great interest. Here, we compare immunization of macaques with mRNA vaccines expressing ancestral spike either including or lacking diproline substitutions, and show the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages.
View Article and Find Full Text PDFFetal exposure to paracetamol (acetaminophen) has been shown to be associated with asthma and other atopic disorders, as well as behavioural problems including hyperactivity, in childhood. However, there is little information on scholastic abilities among children exposed to paracetamol in pregnancy. To determine whether there are any differences in scholastic abilities among the offspring of women who ingested paracetamol during pregnancy compared with non-exposed children.
View Article and Find Full Text PDFAllergy Asthma Clin Immunol
November 2023
Background: Childhood atopic dermatitis can have a negative effect on caregivers' quality of life and stress levels due to the burdensome nature of its treatment. Given that the condition often emerges in infancy, atopic dermatitis-related stress also carries the potential to negatively affect the developing mother-infant bond. While it is plausible that atopic dermatitis has a negative impact on maternal-infant bonding, these relationships have not been studied directly.
View Article and Find Full Text PDFWithin human epidemiological studies, associations have been demonstrated between grandparental exposures during childhood and grandchildren's outcomes. A few studies have assessed whether asthma has ancestral associations with exposure to cigarette smoking, but results have been mixed so far. In this study we used four generations: (F0 great-grandparents, F1 grandparents, F2 parents, F3 study children) of the Avon Longitudinal Study of Parents and Children (ALSPAC) to determine whether there is evidence of associations between asthma in generations F2 or F3 and exposures to severe trauma in childhood and/or active cigarette smoking during the adolescence of grandmothers and grandfathers in generations F0 and F1 respectively, or of a history of a F0 or F1 grandmother smoking during pregnancy.
View Article and Find Full Text PDFBrucellosis is a disease caused by the bacterium Brucella and typically transmitted through contact with infected ruminants. It is one of the most common chronic zoonotic diseases and of particular interest to public health agencies. Despite its well-known transmission history and characteristic symptoms, we lack a more complete understanding of the evolutionary history of its best-known species-Brucella melitensis.
View Article and Find Full Text PDFChem Biol Interact
September 2023
BMJ Open
April 2023
Introduction: Digital patient monitoring (DPM) tools can enable more effective clinical care and improved patient outcomes in cancer. However, their broad adoption requires ease of use and demonstration of real-world clinical utility/impact. ORIGAMA (MO42720) is an interventional, open-label, multicountry platform study investigating the clinical utility of DPM tools and specific treatments.
View Article and Find Full Text PDFPrior studies have examined the effects of victim resistance and type of assault (attempted or completed) on perceptions of adult rape cases. However, research has not yet tested whether these findings extend to verdicts rendered in child rape cases, nor has research focused on how perceptions of victim and defendant characteristics in child rape cases may contribute to legal decision-making. In the present study, a 2 (attempted or completed sexual assault) x 3 (victim resistance: verbal-only, verbal with outside interruption, or physical) x 2 (participant sex) between-participant design was used to assess legal decision-making involving a hypothetical criminal case of child rape, with a six-year-old female victim and a 30-year-old male perpetrator.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) in humans, has a wide host range, naturally infecting felids, canids, cervids, rodents and mustelids. Transmission of SARS-CoV-2 is universally accepted to occur via contact with contaminated secretions from the respiratory epithelium, either directly or indirectly. Transmission via droplet nuclei, generated from a cough or sneeze, has also been reported in several human and experimental animal scenarios.
View Article and Find Full Text PDFVaccine platforms enable fast development, testing, and manufacture of more affordable vaccines. Here, we evaluated Generalized Modules for Membrane Antigens (GMMA), outer membrane vesicles (OMVs) generated by genetically modified Gram-negative bacteria, as a vaccine platform for viral pathogens. Influenza A virus hemagglutinin (HA), either physically mixed with GMMA (HA+STmGMMA mix), or covalently linked to GMMA surface (HA-STmGMMA conjugate), significantly increased antigen-specific humoral and cellular responses, with HA-STmGMMA conjugate inducing further enhancement than HA+STmGMMA mix.
View Article and Find Full Text PDFCoronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.
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