The development of single or double molecule therapeutics for BoNT will require enhancement of the ability of mAbs to clear BoNT from the blood circulation. In this study, we tested the ability of a novel FP to enhance the neutralizing capacity of BoNT-specific mAbs at the level of the blood circulation. The FP is a bifunctional molecule that allows the adherence of biotin-conjugated immune complexes to the RBC surface. The FP was able to significantly increase the neutralization potency of BoNT-specific mAbs. When combined with the FP, the non-neutralizing 13A and 30B mAbs were able to fully neutralize lethal doses of BoNT/A and BoNT/B, respectively. The FP increased the quantity of BoNT/A that could be neutralized by the 6A mAb, the 4LCA mAb, and the 6A/4LCA mAb combination. These levels were achieved with much lower quantities of mAbs than we had previously required for protection with naked mAbs. The NIH and the FDA have not yet established a standard for protective efficacy for BoNT passive immune therapies, but we can compare the potency of our FP combinations with the approved BoNT anti-toxins. The human antiserum for use in infants, BabyBig, has a BoNT/A-specific potency of 3,000 LD50/mg. We found that the FP combined with 6A and 4LCA is sufficient to provide neutralization of 10 LD50 BoNT/A for 72 hours and partial protection at 96 hours. This result indicates the presence of physiologically relevant concentrations of the FP:mAb combination in vivo during this time. We also tested the FP:mAb combination in a post-exposure model, in which the FP:Ab was administered following a lethal dose of toxin. An intravenous injection of the combination was able to provide complete protection from a lethal intraperitoneal BoNT dose at 2 hours and partial protection at 4 hours. BoNT distribution experiments have demonstrated that the window of opportunity of exposure of a lethal dose of BoNT is determined by a first-order reaction that depends on the amount of BoNT administered and the period of time that elapses before the countermeasure is administered. Thus, anti-toxins that are sufficient to neutralize an entire circulating dose of BoNT should give the same window of opportunity for post-exposure salvage, and our post-exposure results are comparable to results LY2109761 obtained by others. The proposed mechanism through which the FP augments antibody neutralization activity involves binding of FP:mAb complexes to the RBC surface. Flow cytometry experiments in vitro demonstrated that the FP:mAb complexes are able to bind to erythrocytes and that the complexes serve as a molecular bridge to adhere BoNT to the RBC. Experiments with un-biotinylated antibodies and the FP did not show any enhancement of neutralization. Streptavidin alone did not improve neutralizing activity of biotinylated BoNT antibodies, in comparison to the RBC-targeted FP. Lastly, the levels of BoNT circulating in the plasma of mice that had received the FP in combination with the 4LCA and 6A were lowered.