Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

Abstract

Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n ϭ 33) versus anthrax vaccine adsorbed (AVA; n ϭ 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 Ϯ 58.6) of EF antibodies than AVA (4.2% and 7.8 Ϯ 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines.

The Bacillus cereus Group: Bacillus Species with Pathogenic Potential

“…The AVP vaccine is administered as four doses over 32 weeks with annual boosters. Unlike AVA, AVP contains low levels of LF and EF, and some reports indicate that humoral responses to LF and EF generated by AVP may contribute to toxin neutralization (418, 419).…”

Bacillus anthracis as a biological warfare agent: infection, diagnosis and countermeasures

“…Active vaccination is not a therapeutic process, when the infection already starts but it is an effective tool for either avoiding or at least ameliorating the disease progression. The parts of anthrax toxin, such as protective antigen, spore specifi c antigens and inactivated spores can be chosen for vaccination purpose (66,67). Commercial Anthrax Vaccine Licensed containing culture supernatant of a non-encapsulated strain producing toxin is effective for eliciting antibodies response.…”

Toxin-neutralizing antibodies elicited by naturally acquired cutaneous anthrax are elevated following severe disease and appear to target conformational epitopes

“…For example, we previously identified several protective and non-protective antibody specificities to toxin antigens in anthrax vaccine recipients [20][21][22]. The observation that the Anthrax Vaccine Precipitated preparation contains all three anthrax toxin components, yet lacks toxin activity [23], suggests that important neutralizing epitopes could be lost due to a change in structure or conformation of anthrax toxin components by alum precipitation. Thus, assessment of the fine specificity of the toxin-neutralizing response to native toxin antigens encountered during natural infection may reveal new toxin-neutralizing epitopes.…”