Disparate adjuvant properties among three formulations of “alum” (52.11)

Abstract

Abstract Aluminum salts, commonly referred to as “alum,” are the most common adjuvants in human vaccines and serve as a benchmark in the development of novel adjuvants. Although the mechanisms that promote humoral responses to alum-adsorbed antigens are still enigmatic, alum is thought to induce inflammatory signals that, in turn, promote antibody production. It has been noted that some formulations of alum used in animal studies, notably Imject alum®, are not the chemical equivalents of the aluminum used in human vaccines, raising concerns where Imject serves as the comparator for novel adjuvants. Here, we compared the capacity of Imject alum, Alhydrogel®, and a traditional alum-antigen (Alum-Ag) precipitate to induce humoral responses in mice to the hapten-carrier NP-CGG. Primary humoral responses elicited by Alhydrogel and the Alum-Antigen precipitate were significantly greater than those induced by Imject alum. The three alum formulations elicited comparable responses in terms of acute eosinophil and monocyte infiltration at the immunization site, but neutrophil recruitment by Imject alum was signficantly reduced compared to Alum-Ag precipitate or Alhydrogel. These findings reveal substantial differences in the adjuvant properties and inflammatory effects of distinct alum preparations, an important consideration in the analysis of new adjuvants and mechanistic studies of alum’s adjuvanticity.