The COVID-19 pandemic has created a global call to action to pharmaceutical companies for the development of a suitable vaccine. In the development of such vaccine(s), understanding the biostability and kinetics/thermodynamics of very small and dilute protein solutions is necessary. Thermal stability is important for the performance of proteins and other biostructures within vaccines. Denaturing of protein structure can limit vaccine function and thus reduce effectiveness of any developed vaccine within the pharmaceutical sector.
C-Therm Technologies Ltd. has worked closely with the world-leader in calorimetry, Setaram Instrumentation, for over a decade. With the SETARAM µDSC VII (See Figure 1) equipped with the unique Calvet sensor’s 93-95% heat detection efficiency, small and precise thermodynamic events can be observed at nanomolar concentrations. Compared to traditional pan-style calorimetry instrumentation, the 3D Calvet sensor offers substantially better sensitivity for the purpose of studying vaccine formulations, or thermal stability of finalized products. With increased urgency in the development of a vaccine for COVID-19, the µDSC VII and µSC DSC instrumentation offer flexibility to measure solids, liquids, solutions and more. Different sample cells can provide mixing, or standard isothermal measurement runs, perfect for monitoring enzymatic reactions in kinetic or isothermal measurement modes. Additionally, the µSC DSC offers higher capacity for running multiple samples at the same time, allowing for comparison between different formulations for vaccine or other biomolecule solutions. Compared to other pan style or capillary style DSC instruments, SETARAMs calorimetry offerings provide versatility without compromising sensitivity and have become a benchmark tool for studying thermal stability of vaccine formulations within the pharmaceutical sector.
The unique advantages of the SETARAM microcalorimeters enable resolution of extremely small heat flow signatures, useful in the study of vaccines and biological drugs. In Figure 2, a linear plasmid DNA (0.05 % in5 mM Cacodylat solution) is heated at a rate of 0.2 K/min from 40°C to 110°C. Multiple endotherms are visible on the plot, each attributable to a different DNA segment.1 Lower temperature endotherms correspond sequences in the DNA rich with adenine and thymine (2 hydrogen bonds) whereas the higher temperature endotherms correspond to regions in the DNA high in guanine and cytosine.
In Figure 3, a SETARAM microcalorimeter is used to detect denaturation and agglomeration of dilute IgG in solution. The microcalorimeter’s high sensitivity heat flow detector can easily detect the denaturation peak at a concentration of 1 mg/mL in a PBS buffer solution. The solution was heated from 25°C to 110°C at 1°C/min. A PBS buffer solution with no protein was used as the reference solution. Two superimposed heat flow signals were detected: an exothermic peak attributed to denaturation and an endothermic peak attributed to aggregation. The CALISTO software enables straightforward resolution of each peak.
C-Therm is offering access to its Setaram calorimeter via its lab services in support of research organizations developing COVID-19 vaccines and can lend considerable expertise in outfitting labs with the high sensitivity tools for accelerating the development of vaccines. For more information, please email info@thermalanalysislabs.com or call us at 1 (506) 457-0498.