Effects of stabilizers on the destabilization of proteins upon adsorption to aluminum salt adjuvants.
Excipients for protein-based vaccines are currently identified by evaluating the stability of the protein in solution. In most cases, however, the protein is adsorbed to the surface of an aluminum salt adjuvant in the final vaccine formulation. Previous studies showed that model protein antigens may be structurally altered and less thermally stable upon adsorption to aluminum salt adjuvants [Jones LS, Peek LJ, Power J, Markham A, Yazzie B, Middaugh CR, 2005, J Biol Chem 280:13406-13414]. The work presented herein provides evidence that compounds that stabilize the protein in solution also stabilize the adsorbed protein; however, the stability of the adsorbed protein in the presence of the stabilizer remains lower than that of the protein in solution. Potential implications of the reduced stability on the approach used to select excipients during formulation development are discussed.
Peek
Laura J
LJ
Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, USA.
Martin
Talia T
TT
Elk Nation
Charity
C
Pegram
Shannel A
SA
Middaugh
C Russell
CR
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D017607:Aluminum Compounds / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D005079:Excipients / Q000008:administration & dosage*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry*
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D005079:Excipients; D011506:Proteins; D014612:Vaccines