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

In-vitro characterisation of the phagocytosis and fate of anthrax spores in macrophages and the effects of anti-PA antibody

“…A PA null mutant of the Ames strain was created by a directed signature-tagged mutagenesis procedure in which the pagA locus encoding PA was interrupted by integration of a vector harbouring an erythromycin-resistance cassette (I. Mendelson, unpublished data). Spores were prepared and purified from broth cultures of the strains, as described previously [7,10,11]. The spores were activated by heating at 658C for 30 min [10] and were evaluated by phase microscopy; they were used only if >95% were refractile (ungerminated).…”

“…The latter are manifested as immune serummediated stimulation of phagocytosis of spores by rabbit peritoneal macrophages (MQs) and the inhibition of spore germination in vitro, in the absence of MQs [6]. It was shown recently that antisera and purified Abs to PA similarly inhibited the germination of spores in vitro and enhanced their phagocytosis by murine peritoneal MQs [7]. The presence of spore-associated proteins recognised by anti-PA Abs was detected by electron microscopy and confirmed by immunoblot analysis of spore coat extracts that revealed antigens staining specifically with anti-PA Abs.…”

Protection against anthrax by needle-free mucosal immunization with human anthrax vaccine

“…Therefore, host immunity at the mucosal sites of entry may be effective for protection against inhalational anthrax. Previous studies by Welkos et al have demonstrated that anti-PA antibodies stimulate spore uptake and interfere with germination in macrophage culture and animal models [6,28]. This suggests a potentially protective role of anti-PA antibodies at mucosal surfaces against anthrax spore infection.…”

“…Interestingly, researchers have found that anti-PA antibody specific immunity has anti-spore activity and might play a role in impeding the early stages of infection with B. anthracis spores [6]. The current US human anthrax vaccine, BioThrax™ (Anthrax Vaccine Adsorbed/AVA, BioPort Corporation, Lansing, MI), consists of aluminum hydroxide-adsorbed supernatant material from fermentor cultures of a toxigenic, non-encapsulated strain of B. anthracis.…”

Protective-antigen (PA) based anthrax vaccines confer protection against inhalation anthrax by precluding the establishment of a systemic infection

“…Nonetheless, activities of macrophages in in vitro studies, it has been suggested that these anti-spore activities of anti-PA antibodies could play a role in the protection during the initial stages of B. anthracis infection in vivo. 16,17 To gain insights as to how these PA-based anthrax vaccines confer protection and impact the vegetative growth of B. anthracis infection, we subjected the vaccinated mice to a lethal inhalation spore challenge, with a derivative of B. anthracis 7702 (7702-lux strain) that emanates luminescence exclusively during the vegetative phase of growth 18 and utilized an in vivo bioluminescence imaging system to monitor the progression of infection both temporally and spatially (Fig. 3).…”