Modified polypeptides based on the botulinum neurotoxin A heavy chain containing the double mutation Trp-Tyr->Leu-Ser in the ganglioside binding motif Ser-X-Trp-Tyr do not bind polysialogangliosides and nerve endings. The polypeptides are useful in the preparation of nontoxic vaccines against the effects of C. botulinum infection. The modified polypeptides are also useful as vehicles for the transepithelial delivery of diagnostic and therapeutic entities, through formation of conjugates between the polypeptides and the diagnostic or therapeutic entities.