A Heterologous Multiepitope DNA Prime/Recombinant Protein Boost Immunisation Strategy for the Development of an Antiserum against Micrurus corallinus (Coral Snake) Venom
| Autor: | Paulo Lee Ho, Clara Guerra Duarte, Ricardo Andrez Machado-de-Ávila, Juliana Branco Novo, K.L. Castro, Carlos Chávez-Olórtegui, Inácio L.M. Junqueira-de-Azevedo, Henrique Roman Ramos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Micrurus corallinus Physiology Antivenom Snake Bites Venom Toxicology Pathology and Laboratory Medicine Biochemistry Immune Physiology Vaccines DNA Medicine and Health Sciences Toxins Elapidae Mice Inbred BALB C Vaccines Synthetic Immune System Proteins Crystallography biology Antivenins Physics lcsh:Public aspects of medicine Vaccination Snakes Condensed Matter Physics Recombinant Proteins Nucleic acids Infectious Diseases Vaccines Subunit Vertebrates Physical Sciences Crystal Structure Epitopes B-Lymphocyte Female Snake Venoms Research Article food.ingredient lcsh:Arctic medicine. Tropical medicine DNA recombination lcsh:RC955-962 Toxic Agents Immunology complex mixtures Antibodies 03 medical and health sciences food Neutralization Tests medicine Genetics Animals Technology Pharmaceutical Solid State Physics Micrurus Coral snake 030102 biochemistry & molecular biology Venoms Lethal dose Public Health Environmental and Occupational Health Organisms Biology and Life Sciences Proteins Reptiles lcsh:RA1-1270 DNA medicine.disease biology.organism_classification Snake bites Disease Models Animal 030104 developmental biology |
| Zdroj: | PLoS Neglected Tropical Diseases, Vol 10, Iss 3, p e0004484 (2016) PLoS Neglected Tropical Diseases |
| ISSN: | 1935-2735 1935-2727 |
| Popis: | Background Envenoming by coral snakes (Elapidae: Micrurus), although not abundant, represent a serious health threat in the Americas, especially because antivenoms are scarce. The development of adequate amounts of antielapidic serum for the treatment of accidents caused by snakes like Micrurus corallinus is a challenging task due to characteristics such as low venom yield, fossorial habit, relatively small sizes and ophiophagous diet. These features make it difficult to capture and keep these snakes in captivity for venom collection. Furthermore, there are reports of antivenom scarcity in USA, leading to an increase in morbidity and mortality, with patients needing to be intubated and ventilated while the toxin wears off. The development of an alternative method for the production of an antielapidic serum, with no need for snake collection and maintenance in captivity, would be a plausible solution for the antielapidic serum shortage. Methods and Findings In this work we describe the mapping, by the SPOT-synthesis technique, of potential B-cell epitopes from five putative toxins from M. corallinus, which were used to design two multiepitope DNA strings for the genetic immunisation of female BALB/c mice. Results demonstrate that sera obtained from animals that were genetically immunised with these multiepitope constructs, followed by booster doses of recombinant proteins lead to a 60% survival in a lethal dose neutralisation assay. Conclusion Here we describe that the genetic immunisation with a synthetic multiepitope gene followed by booster doses with recombinant protein is a promising approach to develop an alternative antielapidic serum against M. corallinus venom without the need of collection and the very challenging maintenance of these snakes in captivity. Author Summary Coral snakes are a group of deadly venomous snakes that exhibit a characteristic red, yellow/white, and black coloured banding pattern. Accidents involving these snakes tend to be very severe or even lethal, causing peripheral nervous system depression with muscle paralysis and vasomotor instability. The only acceptable medical treatment for snakebite accidents is the administration of an antivenom, generally produced by immunising horses with the snake venom. Nonetheless, for what concerns the antielapidic serum production in Brazil, the total amount of venom available for horse immunisations is insufficient. This is mainly due to the small size of coral snake glands, their underground life style, combined with its very low survival rates in captivity. Moreover, cases of patients being intubated and ventilated as a consequence of antivenom shortage in USA have also been registered. In this work, we present an alternative method for the development of antielapidic serum, which does not rely upon snake capture. This serum was produced by a heterologous DNA prime—with a multiepitope DNA string coding for the most reactive epitopes from the most abundant toxins of M. corallinus, a coral snake which occupy highly populated areas in Brazil—followed by recombinant multiepitope protein boost immunisation of mice. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|