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Clin Vaccine Immunol 2012 Sep;19(9):1465-73

Structural and Immunological Analysis of Anthrax Recombinant Protective Antigen Adsorbed to Aluminum Hydroxide Adjuvant.

Wagner L, Verma A, Meade BD, Reiter K, Narum DL, Brady RA, Little SF, Burns DL


New anthrax vaccines currently under development are based on recombinant protective antigen (rPA) and formulated with aluminum adjuvant. Because long-term stability is a desired characteristic of these vaccines, an understanding of the effects of adsorption to aluminum adjuvants on the structure of rPA is important. Using both biophysical and immunological techniques, we compared the structure and immunogenicity of freshly prepared rPA-Alhydrogel® formulations to that of formulations stored for three weeks at either room temperature or 37°C in order to assess the changes in rPA structure that might occur upon long term storage on aluminum adjuvant. Intrinsic fluorescence emission spectra of tryptophan residues indicated that some tertiary structure alterations of rPA occurred during storage on Alhydrogel®. Using anti-PA monoclonal antibodies to probe specific regions of the adsorbed rPA molecule, we found that two monoclonal antibodies that recognize epitopes located in domain 1 of PA exhibited increased reactivity to the stored formulations as compared to freshly prepared formulations. Immunogenicity of rPA-Alhydrogel® formulations in mice was assessed by measuring induction of toxin neutralizing antibodies as well as antibodies reactive to 12-mer peptides spanning the length of PA. Mice immunized with freshly prepared formulations developed significantly higher toxin neutralizing antibody titers than mice immunized with the stored preparations. In contrast, sera from mice immunized with stored preparations exhibited increased reactivity to nine 12-mer peptides corresponding to sequences located throughout the rPA molecule. These results demonstrate that storage of rPA-Alhydrogel® formulations can lead to structural alteration of the protein and loss of ability to elicit toxin neutralizing antibodies.

Category: Journal Article
PubMed ID: #22815152 DOI: 10.1128/CVI.00174-12
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2012-03-10 Entry Last Modified: 2012-10-13