Relationship between the strength of antigen adsorption to an aluminum -containing adjuvant and the immune response
Abstract
Adsorption of the antigen to an aluminum-containing adjuvant is considered an important aspect of vaccine formulation. Adsorption is described by two parameters: the maximum amount that can be adsorbed as a monolayer, which is characterized by the adsorptive capacity; and the strength of the adsorption force, which is described by the adsorptive coefficient. Research to date has focused on the adsorptive capacity with the goal of complete adsorption of the antigen. In this study, the relationship between the adsorptive coefficient and immunopotentiation was investigated. Four vaccines were prepared in which the adsorptive coefficient was varied by altering the number of phosphate groups on the antigen (alpha casein and dephosphorylated alpha casein) or the number of surface hydroxyls on the adjuvant (aluminum hydroxide adjuvant and phosphate-treated aluminum hydroxide adjuvant). In vitro elution upon exposure to interstitial fluid or normal human plasma was inversely related to the adsorptive coefficient. The geometric mean antibody titer in mice was also inversely related to the adsorptive coefficient. T-cell activation was not observed in mice that received the vaccine with the greatest adsorptive coefficient (alpha casein/aluminum hydroxide adjuvant). This suggests that antigen processing and presentation to T-cells is impaired when the antigen is adsorbed too strongly. The tightness of binding with aluminum hydroxide adjuvant was modified for recombinant hepatitis B surface antigen and recombinant o-gp140 surface antigen for human immunodeficiency virus type 1 (HIV-1) by treatment of the adjuvant with phosphate anion. As observed with CAS and DP-CAS, the Langmuir adsorption parameters decreased as the concentration of phosphate anion used to treat AH increased. The elution of rHBsAg (adw) was also inversely related to the adsorptive coefficient. Thus, the tightness of binding of phosphorylated antigens in vaccines may be controlled by pretreatment of AH with phosphate anion.
Degree
Ph.D.
Advisors
Hem, Purdue University.
Subject Area
Pharmaceutical sciences
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