A Heterologous Multiepitope DNA Prime/Recombinant Protein Boost Immunisation Strategy for the Development of an Antiserum against Micrurus corallinus (Coral Snake) Venom

Author(s)

Ramos, Henrique Roman ^{[1, 2]} ; Junqueira-de-Azevedo, Inacio de Loiola M. ^[3] ; Novo, Juliana Branco ^[1] ; Castro, Karen ^[4] ; Duarte, Clara Guerra ^[4] ; Machado-de-Avila, Ricardo A. ^[5] ; Chavez-Olortegui, Carlos ^[4] ; Ho, Paulo Lee ^[1]

Affiliation

^[1] Inst Butantan, Ctr Biotecnol, Sao Paulo, SP - Brazil

^[2] Univ Nove Julho, Dept Ciencias Saude, Sao Paulo, SP - Brazil

^[3] Inst Butantan, Ctr Toxinol Aplicada, Sao Paulo, SP - Brazil

^[4] Univ Fed Minas Gerais, Dept Bioquim, Belo Horizonte, MG - Brazil

^[5] Univ Extremo Sul Catarinense, Unidade Acad Ciencias Saude, Criciuma, SC - Brazil

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 10, n. 3 MAR 2016.
• Web of Science Citations: 13

Abstract

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. (AU)

• FAPESP's process: 09/10328-8 - Production of an antielapidic serum by genetic immunization
• Grantee: Henrique Roman Ramos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral