title: Rapid deamidation of recombinant protective antigen when adsorbed on aluminum hydroxide gel correlates with reduced potency of vaccine.
abstract: Deamidation of the recombinant protective antigen (rPA) correlates with decreased effectiveness of the vaccine in protecting against infection by Bacillus anthracis. We present data demonstrating dramatic deamidation of amino acid positions 713 and 719 of rPA adsorbed onto aluminum hydroxide gel, an adjuvant, relative to rPA stored in solution without adjuvant. Although deamidation did not impact total levels of rPA-specific antibodies in a mouse model, it did correlate with a decrease in toxin-neutralizing antibodies. On the basis of these data, we hypothesize that interactions of rPA with aluminum hydroxide gel are destabilizing and are the direct cause of reduced vaccine efficacy.
authors.affiliation: BD Technologies, Research Triangle Park, North Carolina 27709, USA. ajit_dsouza@bd.com
authors.forename: Ajit Joseph M
authors.initials: AJ
authors.lastname: D'Souza
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Mar
authors.forename: Joanne
authors.initials: J
authors.lastname: Huang
authors.forename: Sumit
authors.initials: S
authors.lastname: Majumdar
authors.forename: Brandi M
authors.initials: BM
authors.lastname: Ford
authors.forename: Beverly
authors.initials: B
authors.lastname: Dyas
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Sullivan
mesh_terms: D000327:Adsorption; D000536:Aluminum Hydroxide / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D022122:Anthrax Vaccines / Q000235:genetics / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001408:Bacillus anthracis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D011994:Recombinant Proteins; D000536:Aluminum Hydroxide