Protection of monkeys against the lethal effects of male funnel-web spider (Atrax robustus) venom by immunization with a toxoid.
A stable toxoid was prepared from robustoxin (the lethal polypeptide neurotoxin in the venom of the male funnel-web spider, Atrax robustus) by polymerization with glutaraldehyde. This material was non-toxic in new-born mice. Administration of the toxoid to three Macaca fascicularis monkeys (50-80 micrograms/kg s.c. at 14-day intervals for 8-12 weeks) produced no toxic effects; anti-robustoxin antibodies were detected in serum samples by immunodiffusion tests within 13-27 days. In vivo evidence of successful protection with the toxoid was obtained by challenging the monkeys with male A. robustus venom (50 micrograms/kg i.v.) under anaesthesia with pentobarbitone (one monkey), or with ketamine, halothane and nitrous oxide, 1-26 weeks after the last injection of the toxoid. Only minor respiratory, cardiovascular and skeletal motor disturbances were produced, and all monkeys recovered fully and uneventfully. Challenge with the same dose of venom in non-immunized or robustoxin N-terminal decapeptide ovalbumin conjugate-treated monkeys resulted in typical lethal neurotoxic effects, culminating in severe hypotension or death from circulatory and respiratory failure within 280 min.
School of Chemistry, Macquarie University, North Ryde, N.S.W., Australia.
D D
DD
Sheumack
C A
CA
Phillips
E J
EJ
Mylecharane
I
I
Spence
R
R
Claassens
M R
MR
Brown
A
A
Comis
M E
ME
Howden
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D005976:Glutaral; D006339:Heart Rate / Q000187:drug effects; D005779:Immunodiffusion; D008252:Macaca fascicularis; D051379:Mice; D008969:Molecular Sequence Data; D009498:Neurotoxins / Q000276:immunology* / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology; D012472:Salivation / Q000187:drug effects; D013111:Spider Venoms / Q000276:immunology* / Q000633:toxicity; D013666:Tears / Q000378:metabolism; D014121:Toxoids / Q000276:immunology*
D009498:Neurotoxins; D010446:Peptide Fragments; D013111:Spider Venoms; D014121:Toxoids; C044536:robustoxin; D005976:Glutaral