The desorption of antigens from model aluminum-containing vaccines

Protein adsorption to solid-liquid interfaces has traditionally been considered an irreversible phenomena. This assumption was examined by study of the desorption of various proteins from the hydrophilic surfaces of the aluminum containing vaccine adjuvants. The effects of dilution, ionic strength, and the physical properties of the protein were considered. In addition, the effect of adding phosphate, sulfate or nitrate anions to model aluminum adjuvant containing vaccines at pH 7.4 was studied. The addition of phosphate anion and to a lesser degree sulfate anion caused additional adsorption of positively charged lysozyme by a model vaccine composed of lysozyme adsorbed onto aluminum phosphate adjuvant. The addition of phosphate anion, and to a lesser degree, sulfate anion, caused desorption of negatively charged ovalbumin from a model vaccine composed of ovalbumin adsorbed by aluminum hydroxide adjuvant. Nitrate anion had no effect on either model vaccine. The effect of phosphate or sulfate anions did not change as the model lysozyme-aluminum phosphate vaccine aged but decreased with time in the model ovalbumin-aluminum hydroxide vaccine. The adsorption of phosphate anion was found to lower the isoelectric point of both adjuvants. Thus, one mechanism acting to produce adsorption or desorption may be an increase in the negative surface charge of the aluminum containing adjuvants. This in turn decreased the electrostatic interaction with negatively charged proteins and increased the electrostatic interaction with positively charged proteins. When the pH of a vaccine is changed to very acidic or alkaline conditions, dissolution of the adjuvant surface as well as electrostatics aid in the desorption of the protein. One must take into account the isoelectric points of the adjuvant and protein as well as the pH-solubility profile of the adjuvant when manipulating the pH of the vaccine. Lastly, surfactants were found to have a wide degree of efficacy with regard to protein desorption in the systems studied. In general, the nonionic and zwitterionic type of surfactants caused little protein to desorb from the adjuvants when compared to the ionic surfactants. The ionic surfactants that were most effective in causing desorption were the most powerful denaturants of the protein being considered