The role of antibodies to Bacillus anthracis and anthrax toxin components in inhibiting the early stages of infection by anthrax spores

Vaccines which are efficacious against anthrax, such as the human vaccine, Anthrax Vaccine Absorbed (AVA), contain the protective antigen (PA) compone nt of the anthrax toxins as the major protective immunogen, Although AVA pr otects against inhalational anthrax, the immune responses to and role in pr otection of PA and possibly other antigens have yet to be fully elucidated. Sera from animals immunized with a toxin-producing, unencapsulated live va ccine strain of Bacillus anthracis have been reported to have anti-spore ac tivities associated with the antitoxin humoral response. The authors perfor med studies to determine whether anti-PA antibody (Ab)containing preparatio ns stimulated spore uptake by phagocytes and suppressed the germination of spores in vitro. AVA- and PA-immune sera from several species enhanced the phagocytosis by murine peritoneal macrophages of spores of the virulent Ame s and the Sterne vaccine strains. Antitoxin Abs appeared to contribute sign ificantly, although not solely, to the enhanced uptake. Rabbit antisera to PA purified from either Sterne or a PA-producing pX01-cured recombinant, af finity-purified anti-PA IgG, and monkey antisera to AVA were used to assess the role of anti-PA Abs, Rabbit anti-PA Abs promoted the uptake of spores of the PA-producing strains Sterne, Ames and RP42, a mutant of Sterne produ cing only PA, but not of the pX01-Delta Sterne-1 strain, Delta Ames strain, or RP4, a mutant of Sterne with deletions in the loci encoding PA and the oedema factor (EF) toxin component and producing only the lethal factor tox in component. Rabbit anti-PA and monkey anti-AVA Abs also significantly inh ibited spore germination in vitro compared to preimmune serum or medium. Sp ore-associated proteins recognized by anti-PA Abs were detected by electron microscopy and confirmed by immunoblotting of spore coat extracts. Thus, t he anti-PA Ab-specific immunity induced by AVA has antispore activity and m ight have a role in impeding the early stages of infection with a anthracis spores.