The effect of surface interaction between proteins and aluminum-containing adjuvants on immune response in rabbits
Abstract
This study was undertaken to investigate the surface interaction between proteins and aluminum-containing adjuvants and its effect on immune response in rabbits. Model vaccines containing varying amounts of protein adsorbed by the adjuvant were prepared. An animal study employing a model antigen, lysozyme, was performed to test whether the amount of protein adsorbed by the adjuvant is a significant factor in immune response. The immune response was measured by the amount of antibody production in rabbits with the enzyme-linked immunosorbent assay (ELISA). The results indicated that the phosphate-treated aluminum hydroxide adjuvants demonstrated a significant adjuvant effect as was evidenced by the four-fold titre increase compared to that of the control group (lysozyme solution). However, there was no significant difference in the mean antibody titre between the group that received the formulation containing 90% of lysozyme adsorbed and the group that received the one containing only 10% of lysozyme adsorbed, suggesting that the amount of lysozyme adsorbed by the aluminum hydroxide adjuvant did not measurably affect the antibody production in rabbits. To further support the experimental results, another animal study was conducted to (1) determine if a smaller amount of adsorbed lysozyme (3%) would produce an adjuvant effect, (2) test the hypothesis that aluminum hydroxide adjuvant can directly stimulate the cells involved in the immune response by administering the aluminum hydroxide adjuvant and the lysozyme simultaneously as separate injections at different sites, and (3) compare the adjuvant effect of crystalline aluminum hydroxide adjuvant and amorphous aluminum phosphate adjuvant. The results showed that while a significant adjuvant effect of aluminum hydroxide is observed, it was independent of the degree of adsorption of lysozyme to adjuvant for the range studied (3% to 90%), which is consistent in two separate studies. Thus, the hypothesis that the adsorption of the antigen to the aluminum hydroxide adjuvant is essential for effective adjuvant activity was challenged. The adjuvant effect of aluminum hydroxide adjuvant and aluminum phosphate adjuvant was found to be similar. The hypothesis of a mechanism based on the ability of aluminum-containing adjuvants to directly stimulate the cells involved in the immune response was also called into question.
Degree
Ph.D.
Advisors
Nail, Purdue University.
Subject Area
Immunology|Pharmaceuticals
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