Towards ambient temperature-stable vaccines: the identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay.

As a result of thermal instability, some live attenuated viral (LAV) vaccines lose substantial potency from the time of manufacture to the point of administration. Developing regions lacking extensive, reliable refrigeration ("cold-chain") infrastructure are particularly vulnerable to vaccine failure, which in turn increases the burden of disease. Development of a robust, infectivity-based high throughput screening process for identifying thermostable vaccine formulations offers significant promise for vaccine development across a wide variety of LAV products. Here we describe a system that incorporates thermal stability screening into formulation design using heat labile measles virus as a prototype. The screening of >11,000 unique formulations resulted in the identification of liquid formulations with marked improvement over those used in commercial monovalent measles vaccines, with <1.0 log loss of activity after incubation for 8h at 40°C. The approach was shown to be transferable to a second unrelated virus, and therefore offers significant promise towards the optimization of formulation for LAV vaccine products.

Development and characterization of a porous micro-patterned scaffold for vascular tissue engineering applications.

The fabrication of functional small diameter blood vessel analogs has implications in vascular disease treatment. Current 3D models of the medial vessel layer lack micron-scale topographical cues that have shown promise in vitro by recapitulating native vascular smooth muscle cell (VSMC) behavior. A major obstacle to fabricating 3D scaffolds is maintaining adequate nutrient diffusion to cells. We have developed and characterized porous micro-patterned poly-caprolactone (PCL) scaffolds using a novel technique that integrates soft lithography, melt molding and particulate leaching of polylactic-co-glycolic acid (PLGA) micro/nanoparticles. Scanning electron microscopy showed that PLGA-leached scaffolds have circular pores significantly smaller than the size scale of the grooved surface pattern (48 microm grooves; 5 microm deep; 12 microm spacing). Diffusion of media through PLGA-leached scaffolds was six-fold greater than through non-porous scaffolds, indicating successful introduction of through-pores into PCL by the PLGA leaching technique. VSMC alignment on micro-patterned PLGA-leached scaffolds was similar to that on micro-patterned non-porous scaffolds, indicating no loss in cellular organization on PLGA-leached scaffolds. In contrast, cells seeded on micro-patterned sodium bicarbonate-leached scaffolds remained un-aligned. The ability to micro-pattern cells on porous scaffolds may facilitate the transfer of micro-technology from simple 2D substrates to complex 3D architectures, allowing for tight control over cellular organization in fabricated tissues.