Antibody from mice immunized with DNA encoding the carboxyl-disintegrin and cysteine-rich domain (JD9) of the haemorrhagic metalloprotease, Jararhagin, inhibits the main lethal component of viper venom.
Envenoming by the Brazilian pit viper, Bothrops jararaca, induces extensive local and systemic haemorrhage in humans. The severe and occasionally lethal outcome of envenoming is prevented only by administration of antivenom which is conventionally prepared by hyperimmunization of large animals with an individual venom or a range of venoms. Since snake venoms typically consist of numerous molecules, only some of which are toxic, antivenoms are antigenically crude preparations whose therapeutic value would theoretically be enhanced by restricting antibody specificity to toxic venom molecules. We report here that high-titre IgG antibody from mice immunized by the GeneGun with DNA encoding the carboxy-terminal JD9 domain of Jararhagin, a haemorrhage-inducing metalloprotease in B. jararaca venom, extensively neutralized the main lethal component of B. jararaca venom. This is to our knowledge the first study to apply DNA-based methods to preparation of antivenom; it represents a novel approach with greater immunological specificity and fewer hazards than conventional systems of antivenom production.
Division of Molecular Biology and Immunology, Liverpool School of Tropical Medicine, Liverpool, UK. robharr@liverpool.ac.uk
R A
RA
Harrison
A M
AM
Moura-Da-Silva
G D
GD
Laing
Y
Y
Wu
A
A
Richards
A
A
Broadhead
A E
AE
Bianco
R D
RD
Theakston
D051722:ADAM Proteins; D000818:Animals; D000997:Antivenins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D019470:Biolistics; D017837:Bothrops; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D019483:Disintegrins / Q000235:genetics* / Q000276:immunology*; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D008565:Membrane Proteins; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D000097146:Bothrops jararaca Venom
D051722:ADAM Proteins; D000997:Antivenins; D003435:Crotalid Venoms; D019483:Disintegrins; D007074:Immunoglobulin G; D008565:Membrane Proteins; D008666:Metalloendopeptidases; D019444:Vaccines, DNA; D000097146:Bothrops jararaca Venom; C498316:Adam9 protein, mouse