Coral snake venom carries significant neurotoxicity and human injuries can be severe or even lethal. Despite this, antivenom treatments are scarce due to challenges collecting adequate amounts of venom needed to produce anti-elapidic serum. PLOS Neglected Tropical Diseases highlights exciting new research from the Butantan Institute in Brazil using synthetically designed DNA to produce coral-snake antivenom.
Currently, coral snake antivenom is produced by immunizing horses with the venom and collecting the anti-elapidic serum produced. Despite its high toxicity, venom yield from coral snakes is very low, and the snakes are difficult to keep in captivity. Since 2003, the only FDA-approved coral snake antivenom has been discontinued, leading to patients being hospitalized for treatment while the effects of the venom wear off. A new approach is therefore urgently needed to produce antivenom more efficiently and cheaply.
The researchers identified 5 toxins within the snake venom and used a technique called SPOT-synthesis to identify the sections of the toxin (epitopes) that are recognized by coral snake antivenom antibodies. They then designed two DNA strings that coded for these epitopes and used them to genetically immunize different groups of mice.
The serum collected from the animals, which contained antibodies to the five toxins, was then tested for antivenom capabilities - by mixing with coral snake venom before being administered to healthy mice - and was found to neutralize venom by 40%. To improve on this result, the researchers used recombinant DNA techniques to generate purified recombinant proteins from the designed multiepitope DNA strings, and gave the mice a series of protein booster shots to increase their immune response. This approach resulted in a final serum with 60% neutralization against coral snake venom.
Although the ideal of 100% neutralization was not met, this approach is a fascinating new response to the challenge of reducing stocks of coral snake antivenom. The use of synthetic DNA bypasses the need to capture and keep snakes, a difficult and expensive process. "The fact that a neutralization of 100% could not be observed does not disqualify this approach as a promising alternative method for the development of an anti-elapidic antiserum," explains Dr Ramos, former postdoctoral fellow at Butantan Institute. "It is worth noting that all the neutralization capabilities observed in this work were, as expected, intimately related to the antibody titres." Techniques to increase the yield of antibodies are likely to lead to even higher neutralization rates, producing a much-needed readily available source of coral snake antivenom.
###
Please contact plosntds@plos.org if you would like more information about our content and specific topics of interest.
All works published in PLOS Neglected Tropical Diseases are open access, which means that everything is immediately and freely available. Use this URL in your coverage to provide readers access to the paper upon publication:
http://dx.plos.org/10.1371/journal.pntd.0004484 (Link goes live upon article publication)
Contact: Henrique Roman Ramos, +55 11 981476230, ramoshr@me.com
Funding: PLH's lab is supported by FAPESP, CNPq and Fundação Butantan grants. HRR's was supported by a FAPESP PostDoc Scholarship (# 09/10328-8). CCO's lab is supported by CAPES, CNPq and FAPEMIG grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
About PLOS Neglected Tropical Diseases
PLOS Neglected Tropical Diseases is a peer-reviewed, open-access journal devoted to the pathology, epidemiology, prevention, treatment, and control of the neglected tropical diseases, as well as public policy relevant to this group of diseases. All works published in PLOS Neglected Tropical Diseases are open access, which means that everything is immediately and freely available subject only to the condition that the original authorship and source are properly attributed. The Public Library of Science uses the Creative Commons Attribution License, and copyright is retained by the authors.
About the Public Library of Science
The Public Library of Science (PLOS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org.
Media Permissions
PLOS Journals publish under a Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits free reuse of all materials published with the article, so long as the work is cited (e.g., Kaltenbach LS et al. (2007) Huntington Interacting Proteins Are Genetic Modifiers of Neurodegeneration. PLOS Genet 3(5): e82. doi:10.1371/journal.pgen.0030082). No prior permission is required from the authors or publisher. For queries about the license, please contact the relative journal contact indicated here: http://www.plos.org/journals/embargopolicy.php
Journal
PLoS Neglected Tropical Diseases