A study of physico-chemical interactions between Haemophilus influenzae type b and meningococcus group C conjugate vaccines.

Background: Haemophilus influenzae type b (Hib) and Meningococcal group C (MenC) conjugate vaccines, which protect against otitis media, bacteremia and invasive diseases, including pneumonia and meningitis, are attractive candidates for combination, since they are both administered to infants and children. A Hib-MenC combination booster at 12 mo has recently been introduced in the U.K. Objectives: To rule out the possibility for the individual vaccine components in a Hib-MenC combination to interact, rendering one or both of them less effective, this work assessed whether these two saccharide-protein conjugates, namely, Hib oligosaccharide-CRM197 (Cross-Reacting Material 197) and MenC-CRM197, interact in solution. Furthermore an evaluation of the size and integrity of the vaccines was also performed. Methods: HPLC Size-exclusion chromatography (SEC) with UV-adsorption and refractive index detection was performed with a phosphate and non-phosphate saline buffer to characterize the size of Hib and MenC conjugates as individual components or when combined. Results: Hib-CRM197 eluted significantly earlier than MenC-CRM197 in both phosphate-saline and MOPS-saline buffers on a TSK5000 PWXL column. When combined, there was no significant change in their elution. Refractive index monitoring showed no evidence of significant free saccharide or free protein. Conclusions: By size-exclusion chromatography and refractive index detection methods, there was no indication of degradation, and no evidence of significant associative interactions between Hib-CRM197 and MenC-CRM197 in saline-based buffers, pH 7.2. African Health Sciences Vol. 7 (4) 2007: pp.190-19

Evidences of Bolgiano scaling in 3D Rayleigh-Benard convection

We present new results from high-resolution high-statistics direct numerical simulations of a tri-dimensional convective cell. We test the fundamental physical picture of the presence of both a Bolgiano-like and a Kolmogorov-like regime. We find that the dimensional predictions for these two distinct regimes (characterized respectively by an active and passive role of the temperature field) are consistent with our measurements.Comment: 4 pages, 3 figure

A prospective study of von Willebrand factor levels and bleeding in pregnant women with type 1 von Willebrand disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134934/1/hae13086.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134934/2/hae13086_am.pd

Quantitative Influence of ABO Blood Groups on Factor VIII and Its Ratio to von Willebrand Factor, Novel Observations from an ARIC Study of 11,673 Subjects

ABO blood groups are known to influence the plasma level of von Willebrand factor (VWF), but little is known about the relationship between ABO and coagulation factor VIII (FVIII). We analyzed the influence of ABO genotypes on VWF antigen, FVIII activity, and their quantitative relationship in 11,673 participants in the Atherosclerosis Risk in Communities (ARIC) study. VWF, FVIII, and FVIII/VWF levels varied significantly among O, A (A1 and A2), B and AB subjects, and the extent of which varied between Americans of European (EA) and African (AA) descent. We validated a strong influence of ABO blood type on VWF levels (15.2%), but also detected a direct ABO influence on FVIII activity (0.6%) and FVIII/VWF ratio (3.8%) after adjustment for VWF. We determined that FVIII activity changed 0.54% for every 1% change in VWF antigen level. This VWF-FVIII relationship differed between subjects with O and B blood types in EA, AA, and in male, but not female subjects. Variations in FVIII activity were primarily detected at low VWF levels. These new quantitative influences on VWF, FVIII and the FVIII/VWF ratio help understand how ABO genotypes differentially influence VWF, FVIII and their ratio, particularly in racial and gender specific manners

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India