Furthermore, we observed that administration of Ang-1 prevented the increase in the pro-inflammatory cytokine IL-1b in lungs of HVT-ventilated mice. Our data may suggest that the role of IL-1b might be less important in the development of vascular leakage during HVT- ventilation.Adherence of the FP-containing complexes to the surface of the RBCs. The observation that the intrinsic neutralization capacity of the naked mAbs correlated directly with the potency level achieved when bound to the FP supports the idea that the FP:mAb:BoNT complexes remain in circulation for a significant period of time before they are definitively removed. In this model, relatively rapid adherence of FP:mAb:BoNT to the RBC membrane would be followed by a slower phase, in which either complex-bound toxin is removed from the RBC surface or the BoNT-bound RBCs are removed from the circulation. This is distinct from clearance of C3b-opsonized immune complexes, which are definitively taken up by the liver and spleen in less than 15 minutes. While circulating and adherent to RBCs, the FP:mAb complexes would be in competition with the neuromuscular junction for BoNT. Intoxication may result from dissociation of BoNT from the antibody complex, or of the FP:mAb:BoNT complex from the surface of the RBC. The high potency of the FP:6A/4LCA complex may partly result from stabilization of BoNT on the RBC surface through cooperative mAb avidity effects, as maximal neutralization with the 4LCA and 6A antibodies was only observed when both were biotinylated. Accelerated RBC destruction is not likely to be a factor in BoNT clearance, as mice treated with FP do not exhibit a reduced hematocrit. Our study has shown the value of immunoadherence as an effective mechanism for improving the neutralizing ability of BoNT mAbs. The potency of the FP:mAb complexes and their utility in the pre-exposure setting demonstrated that immunoadherent immune complexes could be used to protect those at risk of BoNT exposure, in addition to those already exposed. In practice, the FP could be held in a biodefense stockpile as a non-specific immune adjuvant, to be combined with biotinylated MAb specific for the toxin to which people have been exposed. Alternatively, FP sequences could be used to create hybrid MAb molecules that combine, in a single polypeptide, RBC immunoadherent and antitoxin activities in a single construct. An important advantage of the FP is that it can be ligated quickly and irreversibly to any molecule that has been biotinylated. This allows the creation of immunoadherent complexes without having to synthesize novel fused polypeptides or add synthetic linkers.