title: Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants.
abstract: The only US-licensed anthrax vaccine for human use, as well as several experimental vaccines containing solely purified recombinant protective antigen (rPA), are formulated using aluminum hydroxide (Al(OH)3) as an adjuvant. It has been suggested that effective adjuvanticity of aluminum salts for protein antigens depends, at least partially, on the degree of adsorption of the antigen to the adjuvant. On the other hand, the ease of antigen desorption from the adjuvant in a quantitative fashion may facilitate the assessment of vaccine characteristics in the laboratory. In this regard, aluminum phosphate (AlPO4), although deemed a "weaker" adjuvant than Al(OH)3, appears superior to the latter. To investigate the possibility of formulating rPA vaccines with AlPO4, as well as the significance of the adsorption of this antigen to the aluminum salt for adjuvanticity, we studied the effect of AlPO4 and Al(OH)3 on the induction of anti-rPA antibodies in mice. In a first immunization experiment the adjuvanticity of AlPO4 combined with rPA was examined. Antibodies against rPA were measured using an ELISA. Results indicated that AlPO4 is able to significantly increase the antibody response to rPA, irrespective of its degree of adsorption to the adjuvant. Based on these results, in a second experiment mice were immunized twice, with different formulations of rPA containing either AlPO4 or Al(OH)3, and rPA-antibodies were measured using ELISA and an in vitro toxin neutralization assay. Comparable immune responses to rPA were obtained with both aluminum salts. Additionally, results with AlPO4 as adjuvant confirmed that, in this mouse model, binding of the protein to the adjuvant is not essential for adjuvanticity, whereas the amount of adjuvant has an influence on the antibody response induced.
authors.affiliation: Center for Biologics Evaluation and Research, US FDA, CBER/DBPAP [HFM-443], 1401 Rockville Pike, Rockville, MD 20852, USA. ingeberthold@web.de
authors.forename: Inge
authors.initials: I
authors.lastname: Berthold
authors.forename: Maria-Luz
authors.initials: ML
authors.lastname: Pombo
authors.forename: Leslie
authors.initials: L
authors.lastname: Wagner
authors.forename: Juan L
authors.initials: JL
authors.lastname: Arciniega
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D004797:Enzyme-Linked Immunosorbent Assay; D007115:Immunization Schedule; D007525:Isoelectric Focusing; D051379:Mice; D010710:Phosphates / Q000494:pharmacology; D012995:Solubility; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D022122:Anthrax Vaccines; D010710:Phosphates; D014614:Vaccines, Synthetic; D000536:Aluminum Hydroxide; D000535:Aluminum; C012714:aluminum phosphate