| Grant number: | 14/23457-9 |
| Support Opportunities: | Regular Research Grants |
| Start date: | March 01, 2015 |
| End date: | February 28, 2017 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Geraldo Santana Magalhães |
| Grantee: | Geraldo Santana Magalhães |
| Host Institution: | Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Associated researchers: | Ana Maria Moura da Silva ; Katia Cristina Barbaro Nogueira ; Maisa Splendore Della Casa |
Abstract
The venom of the spider Loxosceles is composed of a mixture of toxins that can cause intense inflammatory reaction, dermonecrotic injury, systemic manifestations such as platelet aggregation, hemolytic anemia, and in some cases, acute renal failure. In Brazil, the loxoscelism represented about 27% of the 29 167 cases diagnosed and reported accidents involving spiders (Ministry of Health, 2014) in 2013. To date, there is no global consensus on the treatment for cases of loxoscelism, but in Brazil it is recommended the use of antiarachnid or antiloxoscelico serum. The production of anti-venom serum is through immunization of horses using poisons from animals kept in captivity. However, keeping these animals is costly, extraction of venom is laborious and the quantities obtained are often low. This is particularly relevant in the case of venoms of Loxosceles spiders, which are small and produce few micrograms of venom per individual. For this reason, many studies have explored the use of recombinant toxins or their peptides as immunogens for obtaining neutralizing antibodies against the venom. In this sense, the phospholipase D (PLDS) are among the most studied toxins, because it has been shown to be primarily responsible for the toxic effects observed in loxoscelism. On the other hand, there are also other toxins in the venom that act additively or synergistically to contribute to the damaging effects observed in the envenoming. Thus, studies indicate that the astacin type metalloproteases, which are the second largest class of toxins expressed in the venom gland, have a significant potential in the envenoming and can therefore, be an important immunogen for the production of neutralizing serum. Despite this, to date, it has not been explored the possibility of producing neutralizing antibodies against metalloprotease, as already done for the PLDs. Thus, considering that the PLDs are primarily responsible for the toxic activity of the venom and the metalloproteases represent the second class most expressed toxins in the venom gland, in this project we intend to construct a chimeric recombinant immunogen containing functional regions of the two toxins and use it to produce antibodies in rabbits. These antibodies will be further evaluated about their neutralizing capacity compared to the major toxic effects of the venom of Loxosceles gaucho. Successful, this approach could be applied to obtain other hybrid antigens thus optimizing the production of antivenoms. (AU)
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