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 PDFWe report on discovering the homogeneous boiling within a liquid film residual resting in equilibrium over a melting ice block. This phenomenon was induced via longwave infrared radiation generated by a continuous wave [Formula: see text] laser. This investigation employed a high-speed camera and the Schlieren visualization technique.
View Article and Find Full Text PDFJ Craniovertebr Junction Spine
September 2024
Alloreactive memory T cells have been implicated as central drivers of transplant rejection. Perplexingly, innate cytokines, such as IL-6, IL-1β, and IL-12, are also associated with rejection of organ transplants. However, the pathways of innate immune activation in allogeneic transplantation are unclear.
View Article and Find Full Text PDFInvasive populations often experience founder effects: a loss of genetic diversity relative to the source population, due to a small number of founders. Even where these founder effects do not impact colonization success, theory predicts they might affect the rate at which invasive populations expand. This is because secondary founder effects are generated at advancing population edges, further reducing local genetic diversity and elevating genetic load.
View Article and Find Full Text PDFis a neurotropic single-celled zoonotic parasite that can infect human beings and animals. Infection with is usually asymptomatic in immune-competent individual, however, it can cause symptomatic and life-threatening conditions in immunocompromised individuals and in developing foetuses. Although the mechanisms that allow to persist in host cells are poorly understood, studies in animal models have greatly improved our understanding of -host cell interaction and how this interaction modulates parasite proliferation and development, host immune response and virulence of the parasite.
View Article and Find Full Text PDFThe dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days.
View Article and Find Full Text PDFObjective: This study aimed to quantify both the intra- and intertracer repeatability of lesion-level radiomics features in [Ga]Ga-prostate-specific membrane antigen (PSMA)-11 and [F]F-PSMA-1007 positron emission tomography (PET) scans.
Methods: Eighteen patients with metastatic prostate cancer (mPCa) were prospectively recruited for the study and randomised to one of three test-retest groups: (i) intratracer [Ga]Ga-PSMA-11 PET, (ii) intratracer [F]F-PSMA-1007 PET or (iii) intertracer between [Ga]Ga-PSMA-11 and [F]F-PSMA-1007 PET. Four conventional PET metrics (standardised uptake value (SUV), SUV, SUV and volume) and 107 radiomics features were extracted from 75 lesions and assessed using the repeatability coefficient (RC) and the ICC.
The modes through which individuals disperse prior to reproduction has important consequences for gene flow in populations. In honey bees ( sp.), drones (males) reproduce within a short flight range of their natal nest, leaving and returning each afternoon within a narrow mating window.
View Article and Find Full Text PDFObjective: A ventricle-to-brain index (VBI) >0.35 is associated with low scores on the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) in preterm infants with birth weight <1,250 g. However, VBI obtained at the third ventricle has only moderate interobserver reliability.
View Article and Find Full Text PDFThe dynamics of innate and adaptive immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to SARS-CoV-2 infection in infants and young children in the first weeks and months of life by analyzing blood samples collected before, during, and after infection with Omicron and Non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, were stably maintained for >300 days.
View Article and Find Full Text PDFUnder normal homeostatic conditions, self-double-stranded RNA (self-dsRNA) is modified by adenosine deaminase acting on RNA 1 (ADAR1) to prevent the induction of a type I interferon-mediated inflammatory cascade. Antigen-presenting cells (APCs) sense pathogen-associated molecular patterns, such as dsRNA, to activate the immune response. The impact of ADAR1 on the function of APCs and the consequences to immunity are poorly understood.
View Article and Find Full Text PDFOur previous study using systems vaccinology identified an association between the sterol regulatory binding protein (SREBP) pathway and humoral immune response to vaccination in humans. To investigate the role of SREBP signaling in modulating immune responses, we generated mice with B cell- or CD11c antigen-presenting cell (APC)-specific deletion of SCAP, an essential regulator of SREBP signaling. Ablation of SCAP in CD11c APCs had no effect on immune responses.
View Article and Find Full Text PDFSeveral studies have shown that the pre-vaccination immune state is associated with the antibody response to vaccination. However, the generalizability and mechanisms that underlie this association remain poorly defined. Here, we sought to identify a common pre-vaccination signature and mechanisms that could predict the immune response across 13 different vaccines.
View Article and Find Full Text PDFSystems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses.
View Article and Find Full Text PDFVaccines are among the most cost-effective public health interventions for preventing infection-induced morbidity and mortality, yet much remains to be learned regarding the mechanisms by which vaccines protect. Systems immunology combines traditional immunology with modern 'omic profiling techniques and computational modeling to promote rapid and transformative advances in vaccinology and vaccine discovery. The NIH/NIAID Human Immunology Project Consortium (HIPC) has leveraged systems immunology approaches to identify molecular signatures associated with the immunogenicity of many vaccines.
View Article and Find Full Text PDFResponders to the World Trade Center (WTC) attacks on 9/11/2001 inhaled toxic dust and experienced severe trauma for a prolonged period. Studies report that WTC site exposure duration is associated with peripheral inflammation and risk for developing early-onset dementia (EOD). Free Water Fraction (FWF) can serve as a biomarker for neuroinflammation by measuring in vivo movement of free water across neurons.
View Article and Find Full Text PDFBackground: More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD).
Objective: To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders.
Systemic immunity is stringently regulated by commensal intestinal microbes, including the pathobiont Candida albicans. This fungus utilizes various transcriptional and morphological programs for host adaptation, but how this heterogeneity affects immunogenicity remains uncertain. We show that UME6, a transcriptional regulator of filamentation, is essential for intestinal C.
View Article and Find Full Text PDFThe emergency use authorization of two mRNA vaccines in less than a year from the emergence of SARS-CoV-2 represents a landmark in vaccinology. Yet, how mRNA vaccines stimulate the immune system to elicit protective immune responses is unknown. Here we used a systems vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2).
View Article and Find Full Text PDFEmerging evidence indicates a fundamental role for the epigenome in immunity. Here, we mapped the epigenomic and transcriptional landscape of immunity to influenza vaccination in humans at the single-cell level. Vaccination against seasonal influenza induced persistently diminished H3K27ac in monocytes and myeloid dendritic cells (mDCs), which was associated with impaired cytokine responses to Toll-like receptor stimulation.
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