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

Difference in muscle activation patterns during high-speed versus standard-speed yoga: A randomized sequence crossover study

•Significant differences in EMG were seen between the held and transition phases of a pose.•High-speed yoga produced overall greater electrical activity than low-speed yoga.•High-speed yoga can be used to generate greater muscle utilization. To compare the difference in muscle activation between high-speed yoga and standard-speed yoga and to compare muscle activation of the transitions between poses and the held phases of a yoga pose. Randomized sequence crossover trial A laboratory of neuromuscular research and active aging Interventions: Eight minutes of continuous Sun Salutation B was performed, at a high speed versus a standard-speed, separately. Electromyography was used to quantify normalized muscle activation patterns of eight upper and lower body muscles (pectoralis major, medial deltoids, lateral head of the triceps, middle fibers of the trapezius, vastus medialis, medial gastrocnemius, thoracic extensor spinae, and external obliques) during the high-speed and standard-speed yoga protocols. Main Outcome Measures: Difference in normalized muscle activation between high-speed yoga and standard-speed yoga. Normalized muscle activity signals were significantly higher in all eight muscles during the transition phases of poses compared to the held phases (p<0.01). There was no significant interaction between speed×phase; however, greater normalized muscle activity was seen for highspeed yoga across the entire session. Our results show that transitions from one held phase of a pose to another produces higher normalized muscle activity than the held phases of the poses and that overall activity is greater during highspeed yoga than standard-speed yoga. Therefore, the transition speed and associated number of poses should be considered when targeting specific improvements in performance