Lot-to-lot consistency of a tetravalent dengue vaccine in healthy adults in Australia: a randomised study

Background: The recombinant yellow fever-17D-dengue virus, live, attenuated, tetravalent dengue vac-cine (CYD-TDV) has undergone extensive clinical trials. Here safety and consistency of immunogenicityof phase III manufacturing lots of CYD-TDV were evaluated and compared with a phase II lot and placeboin a dengue-naïve population.Methods: Healthy 18–60 year-olds were randomly assigned in a 3:3:3:3:1 ratio to receive three sub-cutaneous doses of either CYD-TDV from any one of three phase III lots or a phase II lot, or placebo,respectively in a 0, 6, 12 month dosing schedule. Neutralising antibody geometric mean titres (PRNT50GMTs) for each of the four dengue serotypes were compared in sera collected 28 days after the thirdvaccination—equivalence among lots was demonstrated if the lower and upper limits of the two-sided95% CIs of the GMT ratio were ≥0.5 and ≤2.0, respectively.Results: 712 participants received vaccine or placebo and 614 (86%) completed the study; 17 (2.4%) par-ticipants withdrew after adverse events. Equivalence of phase III lots was demonstrated for 11 of 12pairwise comparisons. One of three comparisons for serotype 2 was not statistically equivalent. GMTsfor serotype 2 in phase III lots were close to each other (65.9, 44.1 and 58.1, respectively).Conclusions: Phase III lots can be produced in a consistent manner with predictable immune responseand acceptable safety profile similar to previously characterised phase II lots. The phase III lots maybe considered as not clinically different as statistical equivalence was shown for serotypes 1, 3 and 4across the phase III lots. For serotype 2, although equivalence was not shown between two lots, the GMTsobserved in the phase III lots were consistently higher than those for the phase II lot. As such, in our view,biological equivalence for all serotypes was demonstrated.Joseph Torresi, Leon G. Heron, Ming Qiao, Joanne Marjason, Laurent Chambonneau, Alain Bouckenooghe, Mark Boaz, Diane van der Vliet, Derek Wallace, Yanee Hutagalung, Michael D. Nissen, Peter C. Richmon

Metabolic responses to the acute ingestion of two commercially available carbonated beverages: A pilot study

<p>Abstract</p> <p>Background</p> <p>The purpose of this placebo-controlled, double-blind cross-over study was to compare the effects of two commercially available soft drinks on metabolic rate.</p> <p>Methods</p> <p>After giving informed consent, twenty healthy men and women were randomly assigned to ingest 12 ounces of Celsius™ and, on a separate day, 12 ounces of Diet Coke®. All subjects completed both trials using a randomized, counterbalanced design. Metabolic rate (via indirect calorimetry) and substrate oxidation (via respiratory exchange ratio) were measured at baseline (pre-ingestion) and at the end of each hour for 3 hours post-ingestion.</p> <p>Results</p> <p>Two-way ANOVA revealed a significant interaction (p < 0.001) between trials in metabolic rate. Scheffe post-hoc testing indicated that metabolic rate increased by 13.8% (+ 0.6 L/min, p < 0.001) 1 hr post, 14.4% (+0.63 L/min, p < 0.001) 2 hr post, and 8.5% (+0.37 L/min, p < 0.004) 3 hr post Celsius™ ingestion. In contrast, small (~4–6%) but statistically insignificant increases in metabolic rate were noted following Diet Coke^®ingestion. No differences in respiratory exchange ratio were noted between trials.</p> <p>Conclusion</p> <p>These preliminary findings indicate Celsius™ has thermogenic properties when ingested acutely. The effects of repeated, chronic ingestion of Celsius™ on body composition are unknown at this time.</p

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health

Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis

For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results