Immunization with a synthetic robustoxin derivative lacking disulphide bridges protects against a potentially lethal challenge with funnel-web spider (Atrax robustus) venom

Journal of biosciences

Ewan Mylecharane²  Alfio Comis¹  Ian Spence²  Margaret Tyler³  Merlin Howden4⁴ 

[1] School of Biological and Chemical Sciences, Deakin University, Geelong, Victoria 3217, Australia$$;Department of Pharmacology, University of Sydney, Sydney, NSW 2006, Australia$$;Australian Proteome Analysis Facility, Macquarie University, Sydney, NSW 2109, Australia$$;UNSW Foundation Year, University of New South Wales, Sydney, NSW 2052, Australia$$

关键词: Monkeys;    peptide immunogen;    protection;    spider toxin;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

The venom of male Atrax robustus spiders is potentially lethal to primates. These spiders have been responsible for a number of human deaths. Robustoxin is the lethal toxin in the venom. It is a highly cross-linked polypeptide that has 42 amino acid residues and four disulphide bridges. If these bridges are broken, the resulting polypeptide is nontoxic. Robustoxin was chemically synthesized with all of its eight cysteine residues protected with acetamidomethyl groups in order to avoid formation of disulphide bridges. The resulting derivative was co-polymerized with keyhole limpet haemocyanin. Two Macaca fascicularis monkeys were immunized with this conjugate. The monkeys were challenged, under anaesthesia, with a potentially lethal dose of male A. robustus crude venom. Both monkeys showed some minor symptoms of intoxication but recovered fully with no adverse after-effects. Immunization with the same immunogen, in the absence of keyhole limpet haemocyanin, did not protect a third monkey. The N-terminal 23 amino acid peptide derived from the sequence of robustoxin was synthesized and conjugated with ovalbumin. A fourth monkey was immunized with this conjugate. However, it was not protected against challenge. The implications of these results for the preparation of synthetic peptide vaccines are discussed.

【 授权许可】

Unknown