Paratope diversity in the human antibody response to Bacillus anthracis protective antigen.
The active component of the licensed human anthrax vaccine (BioThrax, or AVA) is a Bacillus anthracis toxin known as protective antigen (PA). Second generation anthrax vaccines currently under development are also based on a recombinant form of PA. Since the current and future anthrax vaccines are based on this toxin, it is important that the immunobiology of this protein in vaccinated humans be understood in detail. We have isolated and analyzed the PA-specific antibody repertoire from an AVA-vaccinated individual. When examined at the clonal level, we find an antibody response that is complex in terms of the combinatorial elements and immunoglobulin variable genes employed. All PA-specific antibodies had undergone somatic hypermutation and class switch recombination, both signs of affinity maturation. Although the antigenic epitopes recognized by the response were distributed throughout the PA monomer, the majority of antibodies arising in this individual following vaccination recognize determinants located on the amino-terminal (PA20) sub-domain of the molecule. This latter finding may have implications for the rational design of future PA-based anthrax vaccines.
Zhou
Jianhui
J
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Ullal
Anuska
A
Liberato
Justine
J
Sun
Jinying
J
Keitel
Wendy
W
Reason
Donald C
DC
D000595:Amino Acid Sequence; D000907:Antibodies, Bacterial / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017578:Immunoglobulin Class Switching; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011995:Recombination, Genetic / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D022801:Complementarity Determining Regions; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; C030325:anthrax toxin
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