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

Abstract

SUMMARYEnvenoming 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.

Transcriptomic basis for an antiserum against Micrurus corallinus (coral snake) venom

“…For practical reasons, in this first evaluation we utilized here a simple intra-muscular protocol, by injecting the DNA in mice in their anterior tibia muscle or quadriceps. Epidermal injection should improve the immune response, as previously demonstrated [ 42 ], particularly if associated with biobalistic protocols. This procedure has already been shown in several studies to be the most efficient to induce an immunological response of the Th2 type (IL-4, IL-5, IL10), efficient to generate more antibodies, which is desirable for hyperimmune serum production.…”

“…Herrmann and colleagues in 2006 [ 44 ] were capable to produce an antiserum in rabbits against anthrax that was capable of neutralizing the deleterious effects of the Bacillus anthracis toxin. Thus, quoting Harrison et al, 2000, [ 42 ]: "The application of DNA-based methodologies to the development of therapeutic antivenom represents the first major conceptual change in antivenom production in over a century and has the potential to provide a more cost-effective, less hazardous and more immunologically specific therapy than those used currently to treat envenoming by snakes"…”

High-throughput immuno-profiling of mamba (Dendroaspis) venom toxin epitopes using high-density peptide microarrays

“…DNA immunisation has been explored by a number of research groups424344454647, as has the use of synthetic epitope strings in the field of spider and scorpion antivenoms48. The possible benefits of using DNA immunisation methods or synthetic epitope strings for immunisation include the independence of snake venoms and the ability to select only the medically important toxins for the immunisation process.…”

Bioinformatics and Multiepitope DNA Immunization to Design Rational Snake Antivenom

“…DNA immunization offers a rational approach to the design of toxin-specific immunotherapy, which we have previously demonstrated to induce titres and protective responses appropriate for antivenom production [ 6 , 7 ] and generate antisera cross-reactive with venoms from phylogenetically distinct viper species and genera [ 8 ]. In light of the above and the sequence conservation of venom toxins, we proposed that a systematic approach to identifying common antigenic epitopes of venom toxins from venom gland EST databases would provide a rational approach to generating interspecific or intergeneric protective antibody responses satisfying the most desirable polyspecific properties of an antivenom.…”