title: The in vitro displacement of adsorbed model antigens from aluminium-containing adjuvants by interstitial proteins.
abstract: Vaccines prepared by adsorbing an antigen onto an aluminium-containing adjuvant are usually administered by intramuscular or subcutaneous injection. The vaccine then comes in contact with interstitial fluid which contains proteins. In vitro displacement studies were performed to determine whether antigens, which are adsorbed to aluminium-containing adjuvants, can be displaced by interstitial proteins. It was found that when previously adsorbed model antigens such as lysozyme or myoglobin were exposed to interstitial proteins such as albumin or fibrinogen that extensive displacement occurred. A factorial study of the displacement of myoglobin from aluminium hydroxide adjuvant by albumin was performed. The displacement occurred rapidly with the majority of the displacement occurring in less than 15 min. Whether the concentration of the adsorbed myoglobin was above or below the adsorptive capacity of the aluminium hydroxide adjuvant affected the amount which could be displaced. Less myoglobin was displaced when the concentration was below the adsorptive capacity. The age of the model vaccine (1, 2 or 7 days) prior to exposure to the interstitial protein did not influence the amount of myoglobin that was displaced. The affinity of model antigens and interstitial proteins for aluminium hydroxide or aluminium phosphate adjuvant was characterized by the adsorption coefficient in the Langmuir equation. In every case studied, the protein having the larger adsorption coefficient was able to displace the protein with the smaller adsorption coefficient.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Heimlich
authors.forename: F E
authors.initials: FE
authors.lastname: Regnier
authors.forename: J L
authors.initials: JL
authors.lastname: White
authors.forename: S L
authors.initials: SL
authors.lastname: Hem
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000327:Adsorption; D000418:Albumins / Q000493:pharmacokinetics; D017607:Aluminum Compounds / Q000493:pharmacokinetics*; D000536:Aluminum Hydroxide / Q000493:pharmacokinetics; D000941:Antigens / Q000378:metabolism*; D005110:Extracellular Space / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D005340:Fibrinogen / Q000493:pharmacokinetics; D007768:Lactalbumin / Q000493:pharmacokinetics; D008956:Models, Chemical; D015233:Models, Statistical; D009113:Muramidase / Q000493:pharmacokinetics; D009211:Myoglobin / Q000493:pharmacokinetics; D010710:Phosphates / Q000493:pharmacokinetics; D011506:Proteins / Q000493:pharmacokinetics*
chemical_list: D000276:Adjuvants, Immunologic; D000418:Albumins; D017607:Aluminum Compounds; D000941:Antigens; D009211:Myoglobin; D010710:Phosphates; D011506:Proteins; D000536:Aluminum Hydroxide; D005340:Fibrinogen; D007768:Lactalbumin; D009113:Muramidase