Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines
Amblyomma sculptum is the main tick associated with human bites in Brazil and the main vector of Rickettsia rickettsii, the causative agent of the most severe form of Brazilian spotted fever. Molecules produced in the salivary glands are directly related to feeding success and vector competence. In...
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Frontiers Media S.A.
2021-02-01
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Series: | Frontiers in Immunology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.611104/full |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Gabriel Cerqueira Alves Costa Izabela Cosso Tavares Ribeiro Otoni Melo-Junior Nelder F. Gontijo Nelder F. Gontijo Mauricio R.V. Sant’Anna Mauricio R.V. Sant’Anna Marcos H. Pereira Marcos H. Pereira Grasielle C.D. Pessoa Grasielle C.D. Pessoa Leonardo B. Koerich Leonardo B. Koerich Fabiano Oliveira Jesus G. Valenzuela Rodolfo Cordeiro Giunchetti Ricardo Toshio Fujiwara Daniella Castanheira Bartholomeu Ricardo N. Araujo Ricardo N. Araujo |
spellingShingle |
Gabriel Cerqueira Alves Costa Izabela Cosso Tavares Ribeiro Otoni Melo-Junior Nelder F. Gontijo Nelder F. Gontijo Mauricio R.V. Sant’Anna Mauricio R.V. Sant’Anna Marcos H. Pereira Marcos H. Pereira Grasielle C.D. Pessoa Grasielle C.D. Pessoa Leonardo B. Koerich Leonardo B. Koerich Fabiano Oliveira Jesus G. Valenzuela Rodolfo Cordeiro Giunchetti Ricardo Toshio Fujiwara Daniella Castanheira Bartholomeu Ricardo N. Araujo Ricardo N. Araujo Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines Frontiers in Immunology Amblyomma sculptum saliva antihemostatic complement inhibitors vaccine |
author_facet |
Gabriel Cerqueira Alves Costa Izabela Cosso Tavares Ribeiro Otoni Melo-Junior Nelder F. Gontijo Nelder F. Gontijo Mauricio R.V. Sant’Anna Mauricio R.V. Sant’Anna Marcos H. Pereira Marcos H. Pereira Grasielle C.D. Pessoa Grasielle C.D. Pessoa Leonardo B. Koerich Leonardo B. Koerich Fabiano Oliveira Jesus G. Valenzuela Rodolfo Cordeiro Giunchetti Ricardo Toshio Fujiwara Daniella Castanheira Bartholomeu Ricardo N. Araujo Ricardo N. Araujo |
author_sort |
Gabriel Cerqueira Alves Costa |
title |
Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines |
title_short |
Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines |
title_full |
Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines |
title_fullStr |
Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines |
title_full_unstemmed |
Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick Vaccines |
title_sort |
amblyomma sculptum salivary protease inhibitors as potential anti-tick vaccines |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-02-01 |
description |
Amblyomma sculptum is the main tick associated with human bites in Brazil and the main vector of Rickettsia rickettsii, the causative agent of the most severe form of Brazilian spotted fever. Molecules produced in the salivary glands are directly related to feeding success and vector competence. In the present study, we identified sequences of A. sculptum salivary proteins that may be involved in hematophagy and selected three proteins that underwent functional characterization and evaluation as vaccine antigens. Among the three proteins selected, one contained a Kunitz_bovine pancreatic trypsin inhibitor domain (named AsKunitz) and the other two belonged to the 8.9 kDa and basic tail families of tick salivary proteins (named As8.9kDa and AsBasicTail). Expression of the messenger RNA (mRNA) encoding all three proteins was detected in the larvae, nymphs, and females at basal levels in unfed ticks and the expression levels increased after the start of feeding. Recombinant proteins rAs8.9kDa and rAsBasicTail inhibited the enzymatic activity of factor Xa, thrombin, and trypsin, whereas rAsKunitz inhibited only thrombin activity. All three recombinant proteins inhibited the hemolysis of both the classical and alternative pathways; this is the first description of tick members of the Kunitz and 8.9kDa families being inhibitors of the classical complement pathway. Mice immunization with recombinant proteins caused efficacies against A. sculptum females from 59.4% with rAsBasicTail immunization to more than 85% by immunization with rAsKunitz and rAs8.9kDa. The mortality of nymphs fed on immunized mice reached 70–100%. Therefore, all three proteins are potential antigens with the possibility of becoming a new tool in the control of A. sculptum. |
topic |
Amblyomma sculptum saliva antihemostatic complement inhibitors vaccine |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2020.611104/full |
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doaj-7fa3011738be41dc8a9857605fdb0daf2021-02-04T05:48:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-02-011110.3389/fimmu.2020.611104611104Amblyomma sculptum Salivary Protease Inhibitors as Potential Anti-Tick VaccinesGabriel Cerqueira Alves Costa0Izabela Cosso Tavares Ribeiro1Otoni Melo-Junior2Nelder F. Gontijo3Nelder F. Gontijo4Mauricio R.V. Sant’Anna5Mauricio R.V. Sant’Anna6Marcos H. Pereira7Marcos H. Pereira8Grasielle C.D. Pessoa9Grasielle C.D. Pessoa10Leonardo B. Koerich11Leonardo B. Koerich12Fabiano Oliveira13Jesus G. Valenzuela14Rodolfo Cordeiro Giunchetti15Ricardo Toshio Fujiwara16Daniella Castanheira Bartholomeu17Ricardo N. Araujo18Ricardo N. Araujo19Laboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Cell-Cell Interactions, Department of Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, BrazilSection of Vector Biology, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesSection of Vector Biology, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesLaboratory of Cell-Cell Interactions, Department of Morphology, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Immunology and Genomics of Parasites, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Immunology and Genomics of Parasites, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratory of Physiology of Hematophagous Insects, Department of Parasitology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular, Rio de Janeiro, BrazilAmblyomma sculptum is the main tick associated with human bites in Brazil and the main vector of Rickettsia rickettsii, the causative agent of the most severe form of Brazilian spotted fever. Molecules produced in the salivary glands are directly related to feeding success and vector competence. In the present study, we identified sequences of A. sculptum salivary proteins that may be involved in hematophagy and selected three proteins that underwent functional characterization and evaluation as vaccine antigens. Among the three proteins selected, one contained a Kunitz_bovine pancreatic trypsin inhibitor domain (named AsKunitz) and the other two belonged to the 8.9 kDa and basic tail families of tick salivary proteins (named As8.9kDa and AsBasicTail). Expression of the messenger RNA (mRNA) encoding all three proteins was detected in the larvae, nymphs, and females at basal levels in unfed ticks and the expression levels increased after the start of feeding. Recombinant proteins rAs8.9kDa and rAsBasicTail inhibited the enzymatic activity of factor Xa, thrombin, and trypsin, whereas rAsKunitz inhibited only thrombin activity. All three recombinant proteins inhibited the hemolysis of both the classical and alternative pathways; this is the first description of tick members of the Kunitz and 8.9kDa families being inhibitors of the classical complement pathway. Mice immunization with recombinant proteins caused efficacies against A. sculptum females from 59.4% with rAsBasicTail immunization to more than 85% by immunization with rAsKunitz and rAs8.9kDa. The mortality of nymphs fed on immunized mice reached 70–100%. Therefore, all three proteins are potential antigens with the possibility of becoming a new tool in the control of A. sculptum.https://www.frontiersin.org/articles/10.3389/fimmu.2020.611104/fullAmblyomma sculptumsalivaantihemostaticcomplement inhibitorsvaccine |