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Toxins 2012, 4(12), 1565-1581; doi:10.3390/toxins4121565
Article

Sheep Monoclonal Antibodies Prevent Systemic Effects of Botulinum Neurotoxin A1

1, 1, 1, 2, 1, 1, 2 and 1,*
Received: 22 November 2012; in revised form: 13 December 2012 / Accepted: 13 December 2012 / Published: 19 December 2012
(This article belongs to the Special Issue Toxin-Antibody Interactions)
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Abstract: Botulinum neurotoxin (BoNT) is responsible for causing botulism, a potentially fatal disease characterized by paralysis of skeletal muscle. Existing specific treatments include polyclonal antisera derived from immunized humans or horses. Both preparations have similar drawbacks, including limited supply, risk of adverse effects and batch to batch variation. Here, we describe a panel of six highly protective sheep monoclonal antibodies (SMAbs) derived from sheep immunized with BoNT/A1 toxoid (SMAbs 2G11, 4F7) or BoNT/A1 heavy chain C-terminus (HcC) (SMAbs 1G4, 5E2, 5F7, 16F9) with or without subsequent challenge immunization with BoNT/A1 toxin. Although each SMAb bound BoNT/A1 toxin, differences in specificity for native and recombinant constituents of BoNT/A1 were observed. Structural differences were suggested by pI (5E2 = 8.2; 2G11 = 7.1; 4F7 = 8.8; 1G4 = 7.4; 5F7 = 8.0; 16F9 = 5.1). SMAb protective efficacy vs. 10,000 LD50 BoNT/A1 was evaluated using the mouse lethality assay. Although not protective alone, divalent and trivalent combinations of SMabs, IG4, 5F7 and/or 16F9 were highly protective. Divalent combinations containing 0.5–4 μg/SMAb (1–8 μg total SMAb) were 100% protective against death with only mild signs of botulism observed; relative efficacy of each combination was 1G4 + 5F7 > 1G4 + 16F9 >> 5F7 + 16F9. The trivalent combination of 1G4 + 5F7 + 16F9 at 0.25 μg/SMAb (0.75 μg total SMAb) was 100% protective against clinical signs and death. These results reflect levels of protective potency not reported previously.
Keywords: botulinum neurotoxin; botulinum toxin; BoNT; BoNT/A1; BoNT/A2; monoclonal antibodies; sheep monoclonal antibodies; immunotherapy; passive immunization; botulism botulinum neurotoxin; botulinum toxin; BoNT; BoNT/A1; BoNT/A2; monoclonal antibodies; sheep monoclonal antibodies; immunotherapy; passive immunization; botulism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Mukherjee, J.; McCann, C.; Ofori, K.; Hill, J.; Baldwin, K.; Shoemaker, C.B.; Harrison, P.; Tzipori, S. Sheep Monoclonal Antibodies Prevent Systemic Effects of Botulinum Neurotoxin A1. Toxins 2012, 4, 1565-1581.

AMA Style

Mukherjee J, McCann C, Ofori K, Hill J, Baldwin K, Shoemaker CB, Harrison P, Tzipori S. Sheep Monoclonal Antibodies Prevent Systemic Effects of Botulinum Neurotoxin A1. Toxins. 2012; 4(12):1565-1581.

Chicago/Turabian Style

Mukherjee, Jean; McCann, Chase; Ofori, Kwasi; Hill, Julia; Baldwin, Karen; Shoemaker, Charles B.; Harrison, Peter; Tzipori, Saul. 2012. "Sheep Monoclonal Antibodies Prevent Systemic Effects of Botulinum Neurotoxin A1." Toxins 4, no. 12: 1565-1581.



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