Forces determining the adsorption of a monoclonal antibody onto an aluminium hydroxide adjuvant: Influence of interstitial fluid components

Selection of Adjuvants for Enhanced Vaccine Potency

“…Two major surface adsorption mechanisms of antigens are known-electrostatic attraction and ligand exchange [39,40]. Both can take place at the same time, but when the antigen and aluminum salts carry the same type of charge (repulsive to each other), ligand exchange plays a key role [41,42].…”

“…The adsorption capacity seems to be limited to a monolayer coverage. This is certainly the case for ligand exchangeominant adsorption of a monoclonal antibody on aluminum hydroxide [40] and hepatitis B surface antigen (HBsAg) on aluminum hydroxide [47]. For hepatitis B surface antigen (HBsAg), the monolayer coverage is at 1.7 mg/mg Al [47].…”

“…The most critical one is arguably the solution pH, as this will determine charged states of antigen and aluminum salts. The influence of pH on antigen adsorption can be complex because of the presence of multiple adsorption mechanisms, and differences in pH-dependent stability of antigens, and solubility of both antigens and aluminum salts [40]. Parabolic pH relationships were reported on lysozyme adsorption on aluminum phosphate (minimum at pH 4) [54] and ovalbumin (pI = 4.7) adsorption on aluminum hydroxide (maximum at pH 4.3-6.2) [55].…”

“…Parabolic pH relationships were reported on lysozyme adsorption on aluminum phosphate (minimum at pH 4) [54] and ovalbumin (pI = 4.7) adsorption on aluminum hydroxide (maximum at pH 4.3-6.2) [55]. In rare cases, maximum adsorption can be found in a pH range, where antigens and aluminum salts carry the same charges [40].…”

“…Presence of phosphate ions in a solution can significantly reduce both the adsorption capacity and coefficient of antigens on aluminum hydroxide due to a variable degree of phosphorylation [42,45]. The adsorption capacity of a monoclonal antibody at pH 7.4 decreased from 1.5 mg/ mg Al in water to 0.14 mg/mg Al in the presence of 100 mM phosphate [40]. The ionic strength of the solution may change the adsorption capacity of an antigen based on electrostatic interactions [40] but should not have a significant effect on ligand exchange-based antigen adsorption [47].…”