title: Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax.
abstract: The immunogenicity of Bacillus anthracis capsule (poly-γ-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >10(3) were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 10(3). An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 10(4) following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT-induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA zchen@niaid.nih.gov.
authors.forename: Zhaochun
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Program in Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Schneerson
authors.affiliation: Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovchik
authors.affiliation: Program in Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Zhongdong
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Program in Developmental and Molecular Immunity, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kubler-Kielb
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Liane
authors.initials: L
authors.lastname: Agulto
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology* / Q000502:physiology; D001427:Bacterial Toxins / Q000276:immunology; D001770:Blood Bactericidal Activity; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D008807:Mice, Inbred BALB C; D050296:Microbial Viability / Q000187:drug effects; D009895:Opsonin Proteins / Q000097:blood; D002679:Pan troglodytes; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000276:immunology; D016019:Survival Analysis; D013745:Tetanus Toxoid / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D009895:Opsonin Proteins; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C030325:anthrax toxin; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid