Anthrax vaccine adsorbed (AVA;
BioThrax), the current FDA-licensed human
anthrax vaccine, contains various amounts of the three
anthrax toxin components, protective
antigen (PA), lethal factor (LF), and
edema factor (EF). While antibody to PA is sufficient to mediate protection against
anthrax in animal models, it is not known if
antibodies to LF or EF contribute to protection in humans. Toxin-neutralizing activity was evaluated in sera from AVA-vaccinated volunteers, all of whom had antibody responses to LF and EF, as well as PA. The contribution of
antibodies to LF and EF was assessed using mouse macrophage J774A.1 cells by examining neutralization of LF-induced lysis using
alamarBlue reduction and neutralization of EF-induced
cyclic AMP increases by
enzyme-linked
immunosorbent assay. Antibody responses to LF and EF were low compared to those to PA, and the amount of LF or EF in the assay could exceed the amount of
antibodies to LF or EF. Higher titers were seen for most individuals when the LF or EF concentration was limiting compared to when LF or EF was in excess, initially suggesting that antibody to LF or EF augmented protection. However, depletion of LF and EF
antibodies in sera did not result in a significant decrease in toxin neutralization. Overall, this study suggests that AVA-induced LF and EF
antibodies do not significantly contribute to
anthrax toxin neutralization in humans and that
antibodies to PA are sufficient to neutralize toxin activity.