title: Differential antibody response to the Anopheles gambiae gSG6 and cE5 salivary proteins in individuals naturally exposed to bites of malaria vectors.
abstract: BACKGROUND
  Mosquito saliva plays crucial roles in blood feeding but also evokes in hosts an anti-saliva antibody response. The IgG response to the Anopheles gambiae salivary protein gSG6 was previously shown to be a reliable indicator of human exposure to Afrotropical malaria vectors. We analyzed here the humoral response to the salivary anti-thrombin cE5 in a group of individuals from a malaria hyperendemic area of Burkina Faso.
  
  
  METHODS
  ELISA was used to measure the anti-cE5 IgG, IgG1 and IgG4 antibody levels in plasma samples collected in the village of Barkoumbilen (Burkina Faso) among individuals of the Rimaibé ethnic group. Anti-gSG6 IgG levels were also determined for comparison. Anopheles vector density in the study area was evaluated by indoor pyrethrum spray catches.
  
  
  RESULTS
  The cE5 protein was highly immunogenic and triggered in exposed individuals a relatively long-lasting antibody response, as shown by its unchanged persistence after a few months of absent or very low exposure (dry season). In addition cE5 did not induce immune tolerance, as previously suggested for the gSG6 antigen. Finally, IgG subclass analysis suggested that exposed individuals may mount a Th1-type immune response against the cE5 protein.
  
  
  CONCLUSIONS
  The anti-cE5 IgG response is shown here to be a sensitive indicator of human exposure to anopheline vectors and to represent an additional tool for malaria epidemiological studies. It may be especially useful in conditions of low vector density, to monitor transiently exposed individuals (i.e. travellers/workers/soldiers spending a few months in tropical Africa) and to evaluate the impact of insecticide treated nets on vector control. Moreover, the gSG6 and cE5 salivary proteins were shown to trigger in exposed individuals a strikingly different immune response with (i) gSG6 evoking a short-lived IgG response, characterized by high IgG4 levels and most likely induction of immune tolerance, and (ii) cE5 eliciting a longer-living IgG response, dominated by anti-cE5 IgG1 antibodies and not inducing tolerance mechanisms. We believe that these two antigens may represent useful reagents to further investigate the so far overlooked role of Anopheles saliva and salivary proteins in host early immune response to Plasmodium parasites.
authors.affiliation: Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. cinzia.rizzo@uniroma1.it.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Rizzo
authors.affiliation: Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. fabrizio.lombardo@uniroma1.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Lombardo
authors.affiliation: Department of Biology, "Federico II" University, Naples, Italy. rafronca@unina.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ronca
authors.affiliation: Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. valentina.mangano@uniroma1.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Mangano
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. s.sirima.cnlp@fasonet.bf.
authors.forename: Sodiomon Bienvenu
authors.initials: SB
authors.lastname: Sirima
authors.affiliation: Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso. issanebie.cnlp@fasonet.bf.
authors.forename: Issa
authors.initials: I
authors.lastname: Nèbiè
authors.affiliation: Department of Biology, "Federico II" University, Naples, Italy. gabriella.fiorentino@unina.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fiorentino
authors.affiliation: Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. david.modiano@uniroma1.it.
authors.forename: David
authors.initials: D
authors.lastname: Modiano
authors.affiliation: Department of Public Health and Infectious Diseases, Division of Parasitology, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. bruno.arca@uniroma1.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Arcà
mesh_terms: D063147:Animal Distribution; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism*; D002677:Chile; D003105:Colombia; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D019476:Insect Proteins / Q000276:immunology*; D007303:Insect Vectors / Q000276:immunology / Q000502:physiology*; D008288:Malaria / Q000635:transmission*; D010865:Pilot Projects; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism*; D014481:United States
chemical_list: D007074:Immunoglobulin G; D019476:Insect Proteins; D012471:Salivary Proteins and Peptides