Portal de Periódicos da CAPES

Salk and Sabin: poliomyelitis immunisation

2004; BMJ; Volume: 75; Issue: 11 Linguagem: Inglês

10.1136/jnnp.2003.028530

1468-330X

J. Pearce,

Biochemical and Structural Characterization

Abstract Snake envenomation is a neglected tropical disease, causing over 100,000 deaths and 300,000 permanent disabilities in humans annually. Here, we recover broadly neutralizing antivenom antibody lineages from the B-cell memory of a human subject with extensive history of snake venom exposure. Centi-3FTX-D09, an antibody from these lineages, recognized a conserved neutralizing epitope on 3-finger toxins (3FTXs), a dominant snake neurotoxin. Crystal structures of Centi-3FTX-D09 in complex with 3FTXs from mamba, taipan, krait, and cobra revealed epitope mimicry of the interface between these neurotoxins and their host target, the nicotinic acetylcholine receptor. Centi-3FTX-D09 provided in-vivo protection against diverse 3FTXs, whole venom challenge from cobras, black mamba, and king cobra, and, when combined with the phospholipase inhibitor varespladib, protection against tiger snake, krait, eastern brown, and taipans.