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

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

Variances of Prediction Errors for Differences of Estimated Genetic Values of Cows in the Same and in Different Herds

A modification of the evaluation method for cows in the northeast United States allowed simultaneous evaluation of cows in pairs of herds and computation of variances of prediction errors of differences of genetic potential between pairs of cows within and across herds. These variances were examined for 20 pairs of herds in Holstein, Jersey, and Brown Swiss breeds. Current evaluations of cows are nearly as accurate for comparing cows from different herds as they are for comparing cows from the same herd

Fluctuations in Sire Evaluations

Large fluctuations in an artificial insemination sire\u27s evaluations concern both dairymen and artificial insemination studs. Characteristics of three bulls with high initial values which dropped on later evaluations were compared with those of 17 normal bulls. Characteristics included genetic yield, management, genetic trend, environmental trend, and size of herds where daughters freshened, genetic merit of mates, and average age at freshening of daughters in first lactation. Evidence suggests that fluctuations are from preferential treatment of daughters of some sires as well as randomness inherent in methods of sampling and evaluating sires

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