title: Formulation of botulinum neurotoxin heavy chain fragments for vaccine development: mechanisms of adsorption to an aluminum-containing adjuvant.
abstract: Heavy chain fragments of botulinum neurotoxin serotypes A and B are being developed as a bivalent vaccine for botulism. To potentiate the immune response, an aluminum containing adjuvant will be formulated with the two antigens. The adsorption mechanisms of each antigen to aluminum phosphate and aluminum hydroxide adjuvants were studied. The adsorption of the serotype A antigen to each adjuvant, and the serotype B antigen to aluminum phosphate adjuvant, is dependent on electrostatic attractive forces. The serotype A antigen is basic, and pretreatment with phosphate anions is required for favorable adsorption conditions to aluminum hydroxide adjuvant. In contrast, the serotype B antigen displays a high affinity to aluminum hydroxide adjuvant even when the two species possess the same charge. It is proposed that the serotype B antigen is adsorbed to aluminum hydroxide adjuvant by a ligand exchange mechanism.
authors.affiliation: Department of Pharmaceutical Sciences and Stability, Diosynth Biotechnology, 101 J. Morris Commons Lane, Morrisville, NC 27560, USA.
authors.forename: Roberto A
authors.initials: RA
authors.lastname: DePaz
authors.forename: Ian
authors.initials: I
authors.lastname: Henderson
authors.forename: Siddharth J
authors.initials: SJ
authors.lastname: Advant
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D017607:Aluminum Compounds / Q000737:chemistry*; D000536:Aluminum Hydroxide / Q000737:chemistry*; D001428:Bacterial Vaccines / Q000737:chemistry* / Q000276:immunology; D001905:Botulinum Toxins / Q000737:chemistry* / Q000276:immunology; D019274:Botulinum Toxins, Type A / Q000276:immunology; D003014:Clostridium botulinum / Q000276:immunology; D019855:Ethylene Glycol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D010446:Peptide Fragments; D010710:Phosphates / Q000737:chemistry*; D011487:Protein Conformation; D012965:Sodium Chloride / Q000737:chemistry; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D001428:Bacterial Vaccines; D010446:Peptide Fragments; D010710:Phosphates; D022223:Vaccines, Subunit; C096323:rimabotulinumtoxinB; D012965:Sodium Chloride; D000536:Aluminum Hydroxide; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; C012714:aluminum phosphate; D019855:Ethylene Glycol