ABSTRACT
Aluminum hydroxide is a critical raw material in the production of many vaccines. It is used as an adjuvant in the formulation of the final bulk vaccine, and for this it must meet the specifications of the European Pharmacopeia Monograph. We investigated whether vaccine stability was affected by the presence of trace amounts of elemental impurities in commercially available aluminum hydroxide. The content of residual elemental impurities in commercially available aluminum hydroxide was determined by selective and sensitive inductively coupled-plasma mass spectrometry and inductively coupled plasma atomic emission spectroscopy. We found significant differences between different suppliers, but also between different lots from the same supplier. Inactivated Japanese encephalitis vaccine, IXIARO(®), was used to study the effect of residual metals in aluminum hydroxide on antigen stability. We propose that antigen degradation occurred via a pathway involving the metal-catalyzed, auto-oxidation of a process-related impurity (sulfite). Thus, sulfite auto-oxidation resulted in antigen degradation when residual Cu was present at elevated concentrations in aluminum hydroxide.
Subject(s)
Adjuvants, Immunologic/chemistry , Aluminum Hydroxide/chemistry , Elements , Japanese Encephalitis Vaccines/chemistry , Vaccine Potency , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Japanese Encephalitis Vaccines/administration & dosage , Japanese Encephalitis Vaccines/immunology , Mass Spectrometry , Mice , Neutralization Tests , Spectrophotometry, Atomic , Viral Plaque AssayABSTRACT
Shielding by four TeCl4 molecules is observed for the distorted rhombic dodecahedron core of the tellurium nitride Te6 N8 (see picture). With the characterization of this structure, the composition of the tellurium nitride discovered 100 years ago has now been determined. As a result of the shielding effect, the explosive character of the nitride is lost.
