ABSTRACT
Objective: We sought to evaluate serum 25-hydroxycholecalciferol (vitamin D [25-OHD]) levels, skin phototype, and sun index in a sample of patients to determine the association between these factors and metabolic risk. Design: This was a cross-sectional study involving 729 adults (50.2% male). Mean age was 65.13±9.18 years, sun index 5.71±5.06, body mass index (BMI) 27.60±5.34 kg/m2, and waist circumference 97.29±12.08cm. Hypertension, metabolic syndrome, and Type 2 diabetes were reported in 77.8, 74.5, and 38.9 percent, respectively; Fitzpatrick Skin Types III and IV were reported in 60.6 percent. Results: Mean serum 25-OHD was 25.72±10.91ng/mL; 31 percent of subjects had serum 25-OHD below 20ng/mL, and 63.1 percent had serum 25-OHD below 30ng/mL. Although there were no significant differences between the vitamin D deficient and sufficient groups regarding age, BMI, waist circumference, or presence of diabetes, in the group with 25-OHD less than 20ng/mL (sun index of 4.5±4.08), higher serum triglycerides and lower high-density lipoprotein cholesterol (HDL-C) levels were measured: triglycerides 179.14±103.53 versus 161.63±90.23mg/dL (p=0.029) and HDL-C 43.48±12.38 versus 45.94±14.14mg/dL (p=0.018) compared to the group with 25-OHD levels of 20ng/mL or higher (sun index: 6.25±5.36). Considering less than 25th percentile (25-OHD: 18.7ng/mL) and 75th percentile or higher (25-OHD: 30.8 ng/mL), the differences in serum triglycerides remained significant: 176.63±103.79 versus 157.47±80.49 (p=0.039). Conclusion: We found a high prevalence of vitamin D deficiency in individuals with high sun exposure, regardless of age, BMI, and waist circumference. This deficiency was associated with increased serum triglycerides and decreased HDL-C levels.
ABSTRACT
Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4(+) T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.
