Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom
Human accidents with spiders of the genus <i>Loxosceles</i> are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to b...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-02-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/11/2/108 |
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| author | Paula A. L. Calabria Lhiri Hanna A. L. Shimokawa-Falcão Monica Colombini Ana M. Moura-da-Silva Katia C. Barbaro Eliana L. Faquim-Mauro Geraldo S. Magalhaes |
| author_facet | Paula A. L. Calabria Lhiri Hanna A. L. Shimokawa-Falcão Monica Colombini Ana M. Moura-da-Silva Katia C. Barbaro Eliana L. Faquim-Mauro Geraldo S. Magalhaes |
| author_sort | Paula A. L. Calabria |
| collection | DOAJ |
| description | Human accidents with spiders of the genus <i>Loxosceles</i> are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant <i>Loxosceles</i> toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen’s formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from <i>Loxosceles gaucho</i>. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by <i>L. gaucho</i>, <i>L. laeta</i>, and <i>L. intermedia</i> venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against <i>Loxosceles</i> ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms. |
| first_indexed | 2024-04-11T22:08:42Z |
| format | Article |
| id | doaj.art-22360fea09084f66a9c7f059e143b31a |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-11T22:08:42Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-22360fea09084f66a9c7f059e143b31a2022-12-22T04:00:37ZengMDPI AGToxins2072-66512019-02-0111210810.3390/toxins11020108toxins11020108Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider VenomPaula A. L. Calabria0Lhiri Hanna A. L. Shimokawa-Falcão1Monica Colombini2Ana M. Moura-da-Silva3Katia C. Barbaro4Eliana L. Faquim-Mauro5Geraldo S. Magalhaes6Laboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilLaboratory of Immunopathology, Butantan Institute, São Paulo 05503-900, BrazilHuman accidents with spiders of the genus <i>Loxosceles</i> are an important health problem affecting thousands of people worldwide. Patients evolve to severe local injuries and, in many cases, to systemic disturbances as acute renal failure, in which cases antivenoms are considered to be the most effective treatment. However, for antivenom production, the extraction of the venom used in the immunization process is laborious and the yield is very low. Thus, many groups have been exploring the use of recombinant <i>Loxosceles</i> toxins, particularly phospholipases D (PLDs), to produce the antivenom. Nonetheless, some important venom activities are not neutralized by anti-PLD antibodies. Astacin-like metalloproteases (ALMPs) are the second most expressed toxin acting on the extracellular matrix, indicating the importance of its inclusion in the antigen’s formulation to provide a better antivenom. Here we show the construction of a hybrid recombinant immunogen, called LgRec1ALP1, composed of hydrophilic regions of the PLD and the ALMP toxins from <i>Loxosceles gaucho</i>. Although the LgRec1ALP1 was expressed as inclusion bodies, it resulted in good yields and it was effective to produce neutralizing antibodies in mice. The antiserum neutralized fibrinogenolytic, platelet aggregation and dermonecrotic activities elicited by <i>L. gaucho</i>, <i>L. laeta</i>, and <i>L. intermedia</i> venoms, indicating that the hybrid recombinant antigen may be a valuable source for the production of protective antibodies against <i>Loxosceles</i> ssp. venoms. In addition, the hybrid recombinant toxin approach may enrich and expand the alternative antigens for antisera production for other venoms.https://www.mdpi.com/2072-6651/11/2/108phospholipases Dmetalloproteases<i>Loxosceles</i> spp.recombinant toxinshybrid immunogenneutralizing antibodiesantivenoms |
| spellingShingle | Paula A. L. Calabria Lhiri Hanna A. L. Shimokawa-Falcão Monica Colombini Ana M. Moura-da-Silva Katia C. Barbaro Eliana L. Faquim-Mauro Geraldo S. Magalhaes Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom Toxins phospholipases D metalloproteases <i>Loxosceles</i> spp. recombinant toxins hybrid immunogen neutralizing antibodies antivenoms |
| title | Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom |
| title_full | Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom |
| title_fullStr | Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom |
| title_full_unstemmed | Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom |
| title_short | Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies against <em>Loxosceles</em> Spider Venom |
| title_sort | design and production of a recombinant hybrid toxin to raise protective antibodies against em loxosceles em spider venom |
| topic | phospholipases D metalloproteases <i>Loxosceles</i> spp. recombinant toxins hybrid immunogen neutralizing antibodies antivenoms |
| url | https://www.mdpi.com/2072-6651/11/2/108 |
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