Immobilisation of vaccines onto micro-crystals for enhanced thermal stability

The thermal instability of many vaccines leads to the wastage of half of all supplied vaccines. In this note, we report the application of a novel technology: protein-coated micro-crystals (PCMC) to improve the thermostability of a model vaccine (diphtheria toxoid, DT). The latter was immobilised onto the surface of a crystalline material (l-glutamine) via a rapid dehydration method, resulting in the production of a fine free-flowing powder. The PCMC consisted of thin, flat crystals with an antigen loading of 3.95% (w/w). The DT-coated glutamine crystals and free DT (the controls) were incubated at different temperatures for a defined time period (4 °C, RT and 37 °C for 2 weeks and 45 °C for 2 days), after which the crystals were suspended in buffer and intramuscularly administered to mice. Incubation of DT (free and crystal-coated) at room temperature and at 37 °C for 2 weeks did not result in any change in the antibody response compared to DT that had always been stored properly (i.e. in the refrigerator). In contrast, incubation of free DT at 45 °C resulted in a reduced IgG response, indicating thermal instability of free DT at that temperature. The antibody response was not reduced, however, with the crystal-coated DT. These preliminary studies show that PCMC is a promising technology for the thermal stabilisation of vaccines.