Commercially available and proprietary aluminum adjuvants are a component in over 20 currently U.S.-licensed vaccines. They have been widely used in vaccines for adults and children because of their high safety profile and effectiveness at triggering a greater immune response to the vaccine. However, aluminum adjuvants make vaccines sensitive to damage upon freezing. For this reason, their storage conditions require a narrow temperature range above freezing, 2-8 °C. When storage violations are observed, entire batches are wasted, and when violations occur but are not observed, people might receive ineffective vaccines or experience adverse reactions. A noninvasive means of detecting changes in product quality at the point-of-care would be beneficial.
We sought to determine whether time-domain (TD) benchtop NMR relaxometry is sensitive to vaccine changes due to freezing stress, which can accidentally occur during vaccine shipment or storage. Not only is the transverse relaxation rate of the water proton, R2(1H2O), sensitive to vaccine freezing, it is sensitive in both the suspension and sedimented state of the vaccine. The R2(1H2O) provided a quantitative measure of product quality where previously the only comparable noninvasive method was visual inspection. Visual inspection is impractical for low volume vaccines such as these (0.5 mL – 1.0 mL) where labels also cover the vial. These results from unopened vaccine vials suggest that benchtop NMR has potential as a quality assurance method for finished vaccine products, especially at the point-of-care.
Furthermore, adjuvant raw materials and vaccine products were characterized by differences in sedimentation rate, measured by R2(1H2O) over time. The sedimentation rate of two adjuvants, Alhydrogel® and Adju-Phos® shows a concentration dependence. Two vaccines, Daptacel®, and Engerix-B®, sedimented faster than their corresponding adjuvants alone at the same Al(III) concentration. The vaccines that experienced freezing stress sedimented faster than vaccines that were stored properly, as was expected; this phenomenon is the basis for the WHO shake test. The R2(1H2O) of an aluminum particle suspension over time provided a quantitative measure of sedimentation rate that could be used in product characterization. These results highlight the usefulness of TD wNMR for the characterization and quality assurance of vaccines and adjuvants.