title: An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor.
abstract: Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF domains were assessed for immunogenicity in mice when given alone or with PA. Based on the results obtained, a novel fusion protein comprising D1 of LF and the host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine protection studies demonstrated that both full-length LF and D1 of LF conferred complete protection against a lethal intraperitoneal challenge with B. anthracis STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar level of protection. LF is immunogenic in humans and is likely to contribute to the protection stimulated by AVP. A single vaccine comprising protective regions from LF and PA would simplify production and confer a broader spectrum of protection than that seen with PA alone.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff, CF10 3NB, Wales, UK. bailliel@Cardiff.ac.uk
authors.forename: Les W
authors.initials: LW
authors.lastname: Baillie
authors.forename: Theresa B
authors.initials: TB
authors.lastname: Huwar
authors.forename: Stephen
authors.initials: S
authors.lastname: Moore
authors.forename: Gabriela
authors.initials: G
authors.lastname: Mellado-Sanchez
authors.forename: Liliana
authors.initials: L
authors.lastname: Rodriguez
authors.forename: Brendan N
authors.initials: BN
authors.lastname: Neeson
authors.forename: Helen C
authors.initials: HC
authors.lastname: Flick-Smith
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Jenner
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Ingram
authors.forename: Danny M
authors.initials: DM
authors.lastname: Altmann
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
mesh_terms: D000818:Animals; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin