Development of Silica-Immobilized Vaccines for Improving Thermo-Tolerance and Shelf-Life

Abstract

It is estimated that 50% of vaccines produced annually are wasted because effectivity is dependent on protein structure and heat exposure disrupts the intermolecular interactions that maintain this structure. Since 90% of vaccines require a temperature-controlled supply chain, it is necessary to create a cold chain system to minimize vaccine waste. We have developed a more sustainable technology via the adsorption of Invasion Plasmid Antigen D (IpaD) onto mesoporous silica gels, improving the thermal stability of protein-based therapeutics. The solution depletion method using UV-Vis was utilized to study the adsorption of IpaD onto silica gels. The silica-IpaD complex is heated above the denaturing temperature of the protein and then the IpaD is removed using N,N-Dimethyldodecylamine N-oxide (LDAO) and their secondary structure is tested using circular dichroism (CD). Pore diameter, pore volume and surface area were characterized for seven different silica gels. Silica gels designated as 6389, 6378, and 6375 had an adsorption percentage above 95% at pore volumes of 2.2, 2.8 and 3.8 cm3 mg-1, respectively. CD analyses confirmed that the adsorbed IpaD after the heat treatment displayed a similar "W" shape CD signal as the native IpaD, indicating the conservation of α-helices. In contrast, the unprotected IpaD after being exposed to high temperature shows a flat CD signal, demonstrating the loss of secondary structure. We have successfully increased the thermo-tolerance for IpaD using mesoporous silica and continue to further optimize mesoporous silica's physiochemical properties to improve adsorption and desorption yields.