Bacillus anthracis capsular conjugates elicit chimpanzee polyclonal antibodies that protect mice from pulmonary anthrax. Academic Article uri icon

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-naïve 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 1-2 weeks following the 1(st) immunization, with no booster effects following 2(nd) and 3(rd) 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 1(st) immunization were ≤300, with the antibodies peaking above 10(4) following the 2(nd) immunization. The polyclonal anti-PGA shared the mAb 11D epitope and, similar to the mAbs, exerted opsonophagocytic killing of B. anthracis. Most importantly, 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 second generation anthrax vaccines.Copyright © 2015, American Society for Microbiology. All Rights Reserved.

publication date

  • June 2015