title: Factors affecting alum-protein interactions.
abstract: Alum (or aluminum-containing) adjuvants are key components of many vaccines currently on the market. The immuno-potentiation effect of alum adjuvants is presumably due to their interaction with antigens, leading to adsorption on the alum particle surface. Understanding the mechanism of antigen adsorption/desorption and its influencing factors could provide guidance on formulation design and ensure proper in-vivo immuno-potentiation effect. In this paper, surface adsorption of several model proteins on two types of aluminum adjuvants (Alhydrogel(®) and Adjuphos(®)) are investigated to understand the underlying adsorption mechanisms, capacities, and potential influencing factors. It was found that electrostatic interactions are the major driving force for surface adsorption of all the model proteins except ovalbumin. Alhydrogel has a significantly higher adsorption capacity than Adjuphos. Several factors significantly change the adsorption capacity of both Alhydrogel and Adjuphos, including molecular weight of protein antigens, sodium chloride, phosphate buffer, denaturing agents, and size of aluminum particles. These important factors need to be carefully considered in the design of an effective protein antigen-based vaccine.
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences, Pfizer Inc., 1 Burtt Rd, Andover, MA 01810, United States. Electronic address: min.huang@pfizer.com.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Pharmaceutical Research and Development, Biotherapeutic Pharmaceutical Sciences,﻿ Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D017607:Aluminum Compounds / Q000737:chemistry*; D000536:Aluminum Hydroxide / Q000737:chemistry*; D000941:Antigens / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D014612:Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D000941:Antigens; D010710:Phosphates; D011506:Proteins; D014612:Vaccines; D011092:Polyethylene Glycols; D000536:Aluminum Hydroxide; C012714:aluminum phosphate
keywords: Adjuvant; Adsorption; Alum; Desorption; Formulation; Protein