ProC6C, a novel multi-stage malaria vaccine, elicits functional antibodies against the minor and central repeats of the Circumsporozoite Protein in human adults.

Introduction: ProC6C is a multi-stage malaria vaccine which includes Circumsporozoite Protein (PfCSP), Pfs48/45 and Pfs230 sequences, designed to elicit functional antibodies that prevent sporozoite invasion of human hepatocytes (PfCSP) and parasite development in mosquitoes (Pfs48/45 and Pfs230). ProC6C formulated on Alhydrogel was evaluated in combination with Matrix-M in a Phase 1 trial in Burkina Faso. The PfCSP antibody responses were assessed for magnitude, specificity, avidity and functionality.

Circulating apoE4 protein levels from dried blood spots predict cognitive function in a large population-based survey setting.

Introduction: The apolipoprotein E (APOE) ε4 allele carries risk for cognitive impairment, but whether the level of circulating apoE4 protein in carriers affects cognition is unclear, as is how health and lifestyle impact circulating apoE4 levels.

Methods: We assayed apoE4 protein levels in dried blood spots of 12,532 adults aged 50+. Regression analyses tested the likelihood of cognitive impairment between groups and within those with detected apoE4 protein.

Maternal pre-pregnancy and prenatal penicillin, neonatal inflammation and growth factors are associated to ADHD in the offspring.

Background: The etiology for Attention Deficit Hyperactivity Disorder (ADHD) is generally unknown, but both genetics, biology and environment have been shown to increase the risk. The purpose of this study was to explore the prenatal risk factors, especially maternal antibiotics consumed before and during pregnancy, for the offspring for later being diagnosed with ADHD, and to find associations with neonatal biomarkers.

Methods: We included new-borns from the CODIBINE study, 465 children were ADHD cases and 10 954 children were controls.

Assessment of circulating apoE4 levels from dried blood spot samples in a large survey setting.

Introduction: The apolipoprotein E () ε4 allele is associated with high risk for Alzheimer's disease. It is unclear whether individual levels of the circulating apoE4 protein in ε4 carriers confer additional risk. Measuring apoE4 protein levels from dried blood spots (DBS) has the potential to provide information on genetic status as well as circulating levels and to include these measures in large survey settings.

Levels of cytokines in the cerebrospinal fluid of patients with psychotic disorders compared to individually matched healthy controls.

Background: Increased peripheral cytokine levels have been observed in patients with psychotic disorders; however, large high-quality studies with individually matched healthy controls have been lacking regarding cytokines in cerebrospinal fluid (CSF) of individuals with psychotic disorders.

Methods: Patients diagnosed with a non-organic, non-affective psychotic disorder (ICD-10: F20/22-29) within a year prior to inclusion and individually age- and sex-matched healthy controls were included by identical in- and exclusion criteria's except for the psychiatric diagnoses. All participants were aged 18-50 years and individuals with neurological or immunological disorders were excluded.

Comparisons of 25 cerebrospinal fluid cytokines in a case-control study of 106 patients with recent-onset depression and 106 individually matched healthy subjects.

Background: Neuroinflammation has been suggested as a contributor to the pathophysiology of depression; however, large case-control studies investigating cytokine levels in the cerebrospinal fluid (CSF) from patients with recent-onset depression by multiplex analyses are missing.

Methods: An individually matched (sex and age) prospective case-control study comparing patients with recent-onset depression to healthy controls. CSF was analyzed with the Mesoscale V-PLEX Neuroinflammation Panel 1.

Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots.

The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes.

Delivery Modality Affect Neonatal Levels of Inflammation, Stress, and Growth Factors.

As part of the study CODIBINE, Correlations and Diagnoses for Biomarkers in New-borns, the main objective of the study was to explore neonatal inflammation, stress, neurodevelopment, and growth factors after in-labor and pre-labor cesarean section compared to vaginal delivery. Increasing evidence has shown that birth delivery mode has an impact on imminent and long-term child health. However, the effect of the timing of cesarean section is insufficiently elucidated.

Preterm Birth Is Associated With Immune Dysregulation Which Persists in Infants Exposed to Histologic Chorioamnionitis.

Introduction: Preterm infants are at increased risk of exposure to histologic chorioamnionitis (HCA) when compared to term-born controls, and this is associated with several neonatal morbidities involving brain, lungs and gut. Preterm infants could benefit from immunomodulatory therapies in the perinatal period, but development of rational treatment strategies requires improved characterization of the perinatal response to HCA. We had two objectives: The first, to characterize the umbilical cord blood immune profile in preterm infants compared to term-born controls; the second, to investigate the postnatal immune response in preterm infants exposed to HCA versus those who were not.

The effect of pre-analytical handling on the stability of fractalkine, monocyte chemoattractant protein 1 (MCP1), interleukin 6 and interleukin 8 in samples of human cerebrospinal fluid.

Cytokine networks in cerebrospinal fluid (CSF) are important to our understanding of several neuroinflammatory diseases. Knowledge about optimal handling of samples is limited but important to minimize bias and reduce costs in CSF biomarker studies. The aim of this study was to examine the effect of storage temperature and time delay from CSF sample collection until freezing on the concentration of 11 different cytokines thought to be associated with chronic pain.

Interleukin-8 dysregulation is implicated in brain dysmaturation following preterm birth.

Background: Preterm birth is associated with dysconnectivity of structural brain networks, impaired cognition and psychiatric disease. Systemic inflammation contributes to cerebral dysconnectivity, but the immune mediators driving this association are poorly understood. We analysed information from placenta, umbilical cord and neonatal blood, and brain MRI to determine which immune mediators link perinatal systemic inflammation with dysconnectivity of structural brain networks.

Secretion of parathyroid hormone may be coupled to insulin secretion in humans.

Objective: Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.

Reduced neonatal brain-derived neurotrophic factor is associated with autism spectrum disorders.

Mental disorders have for the majority of cases an unknown etiology, but several studies indicate that neurodevelopmental changes happen in utero or early after birth. We performed a nested case-control study of the relation between blood levels of neuro-developmental (S100B, BDNF, and VEGF-A) and inflammatory (MCP-1, TARC, IL-8, IL-18, CRP, and IgA) biomarkers in newborns, and later development of autism spectrum disorders (ASD, N = 751), attention deficit hyperactivity disorders (ADHD, N = 801), schizophrenia (N = 1969), affective (N = 641) or bipolar disorders (N = 641). Samples and controls were obtained as part of the iPSYCH Danish Case-Cohort Study using dried blood spot samples collected between 1981 and 2004, and stored frozen at the Danish National Biobank.