Differential antibody response to the Anopheles gambiae gSG6 and cE5 salivary proteins in individuals naturally exposed to bites of malaria vectors.

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

Wide cross-reactivity between Anopheles gambiae and Anopheles funestus SG6 salivary proteins supports exploitation of gSG6 as a marker of human exposure to major malaria vectors in tropical Africa

<p>Abstract</p> <p>Background</p> <p>The <it>Anopheles gambiae </it>gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector <it>A. gambiae</it>. However, malaria transmission in tropical Africa is sustained by three main vectors (<it>A. gambiae</it>, <it>Anopheles arabiensis </it>and <it>Anopheles funestus</it>) and a general marker, reflecting exposure to at least these three species, would be especially valuable. The SG6 protein is highly conserved within the <it>A. gambiae </it>species complex whereas the <it>A. funestus </it>homologue, fSG6, is more divergent (80% identity with gSG6). The aim of this study was to evaluate cross-reactivity of human sera to gSG6 and fSG6.</p> <p>Methods</p> <p>The <it>A. funestus </it>SG6 protein was expressed/purified and the humoral response to gSG6, fSG6 and a combination of the two antigens was compared in a population from a malaria hyperendemic area of Burkina Faso where both vectors were present, although with a large <it>A. gambiae </it>prevalence (>75%). Sera collected at the beginning and at the end of the high transmission/rainy season, as well as during the following low transmission/dry season, were analysed.</p> <p>Results</p> <p>According to previous observations, both anti-SG6 IgG level and prevalence decreased during the low transmission/dry season and showed a typical age-dependent pattern. No significant difference in the response to the two antigens was found, although their combined use yielded in most cases higher IgG level.</p> <p>Conclusions</p> <p>Comparative analysis of gSG6 and fSG6 immunogenicity to humans suggests the occurrence of a wide cross-reactivity, even though the two proteins carry species-specific epitopes. This study supports the use of gSG6 as reliable indicator of exposure to the three main African malaria vectors, a marker which may be useful to monitor malaria transmission and evaluate vector control measures, especially in conditions of low malaria transmission and/or reduced vector density. The <it>Anopheles stephensi </it>SG6 protein also shares 80% identity with gSG6, suggesting the attractive possibility that the <it>A. gambiae </it>protein may also be useful to assess human exposure to several Asian malaria vectors.</p

Swift XRT Observations of the Afterglow of XRF 050416A

Swift discovered XRF 050416A with the BAT and began observing it with its narrow field instruments only 64.5 s after the burst onset. Its very soft spectrum classifies this event as an X-ray flash. The afterglow X-ray emission was monitored up to 74 days after the burst. The X-ray light curve initially decays very fast, subsequently flattens and eventually steepens again, similar to many X-ray afterglows. The first and second phases end about 172 and 1450 s after the burst onset, respectively. We find evidence of spectral evolution from a softer emission with photon index Gamma ~ 3.0 during the initial steep decay, to a harder emission with Gamma ~ 2.0 during the following evolutionary phases. The spectra show intrinsic absorption in the host galaxy. The consistency of the initial photon index with the high energy BAT photon index suggests that the initial phase of the X-ray light curve may be the low-energy tail of the prompt emission. The lack of jet break signatures in the X-ray afterglow light curve is not consistent with empirical relations between the source rest-frame peak energy and the collimation-corrected energy of the burst. The standard uniform jet model can give a possible description of the XRF 050416A X-ray afterglow for an opening angle larger than a few tens of degrees, although numerical simulations show that the late time decay is slightly flatter than expected from on-axis viewing of a uniform jet. A structured Gaussian-type jet model with uniform Lorentz factor distribution and viewing angle outside the Gaussian core is another possibility, although a full agreement with data is not achieved with the numerical models explored.Comment: Accepted for publication on ApJ; replaced with revised version: part of the discussion moved in an appendix; 11 pages, 6 figures; abstract shortened for posting on astro-p

Novel Insights Into the Protective Role of Hemoglobin S and C Against Plasmodium falciparum Parasitemia.

Although hemoglobin S (HbS) and hemoglobin C (HbC) are well known to protect against severe Plasmodium falciparum malaria, conclusive evidence on their role against infection has not yet been obtained. Here we show, in 2 populations from Burkina Faso (2007-2008), that HbS is associated with a 70% reduction of harboring P. falciparum parasitemia at the heterozygous state (odds ratio [OR] for AS vs AA, 0.27; 95% confidence interval [CI], .11-.66; P = .004). There is no evidence of protection for HbC in the heterozygous state (OR for AC vs AA, 1.49; 95% CI, .69-3.21; P = .31), whereas protection even higher than that observed with AS is observed in the homozygous and double heterozygous states (OR for CC + SC vs AA, 0.04; 95% CI, .01-.29; P = .002). The abnormal display of parasite-adhesive molecules on the surface of HbS and HbC infected erythrocytes, disrupting the pathogenic process of sequestration, might displace the parasite from the deep to the peripheral circulation, promoting its elimination at the spleen level

Lack of Association of Interferon Regulatory Factor 1 with Severe Malaria in Affected Child-Parental Trio Studies across Three African Populations

Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in both innate and adaptive responses against intracellular pathogens such as Plasmodium falciparum. Polymorphisms at the human IRF1 locus have been previously found to be associated with the ability to control P. falciparum infection in populations naturally exposed to malaria. In order to test whether genetic variation at the IRF1 locus also affects the risk of developing severe malaria, we performed a family-based test of association for 18 Single Nucleotide Polymorphisms (SNPs) across the gene in three African populations, using genotype data from 961 trios consisting of one affected child and his/her two parents (555 from The Gambia, 204 from Kenya and 202 from Malawi). No significant association with severe malaria or severe malaria subphenotypes (cerebral malaria and severe malaria anaemia) was observed for any of the SNPs/haplotypes tested in any of the study populations. Our results offer no evidence that the molecular pathways regulated by the transcription factor IRF-1 are involved in the immune-based pathogenesis of severe malaria

Swift XRT Observations of the Afterglow of GRB 050319

Swift discovered the high redshift GRB 050319 with the Burst Alert Telescope and began observing with its narrow field instruments only 225 s after the burst onset. The afterglow X-ray emission was monitored by the XRT up to 28 days after the burst. The light curve shows a decay with three different phases, each characterized by a distinct slope: an initial steep decay with a power law index of ~ 5.5, a second phase characterized by a flat decay slope of \~ 0.54, and a third phase with a decay slope of ~ 1.14. During the first phase the spectral energy distribution is softer than in the following two phases and the photon index is consistent with the GRB prompt spectrum. The extrapolation of the BAT light curve to the XRT band suggests that the initial fast decaying phase of the XRT afterglow might be the low energy tail of the prompt emission. The second break in the afterglow light curve occurs about 27000 s after the burst. The spectral energy distribution before and after the second break does not change and it can be tentatively interpreted as a jet break or the end of a delayed or continuous energy injection phase.Comment: 15 pages, 2 figures. Accepted for publication in Ap

Humoral Response to the Anopheles gambiae Salivary Protein gSG6: A Serological Indicator of Exposure to Afrotropical Malaria Vectors

Salivary proteins injected by blood feeding arthropods into their hosts evoke a saliva-specific humoral response which can be useful to evaluate exposure to bites of disease vectors. However, saliva of hematophagous arthropods is a complex cocktail of bioactive factors and its use in immunoassays can be misleading because of potential cross-reactivity to other antigens. Toward the development of a serological marker of exposure to Afrotropical malaria vectors we expressed the Anopheles gambiae gSG6, a small anopheline-specific salivary protein, and we measured the anti-gSG6 IgG response in individuals from a malaria hyperendemic area of Burkina Faso, West Africa. The gSG6 protein was immunogenic and anti-gSG6 IgG levels and/or prevalence increased in exposed individuals during the malaria transmission/rainy season. Moreover, this response dropped during the intervening low transmission/dry season, suggesting it is sensitive enough to detect variation in vector density. Members of the Fulani ethnic group showed higher anti-gSG6 IgG response as compared to Mossi, a result consistent with the stronger immune reactivity reported in this group. Remarkably, anti-gSG6 IgG levels among responders were high in children and gradually declined with age. This unusual pattern, opposite to the one observed with Plasmodium antigens, is compatible with a progressive desensitization to mosquito saliva and may be linked to the continued exposure to bites of anopheline mosquitoes. Overall, the humoral anti-gSG6 IgG response appears a reliable serological indicator of exposure to bites of the main African malaria vectors (An. gambiae, Anopheles arabiensis and, possibly, Anopheles funestus) and it may be exploited for malaria epidemiological studies, development of risk maps and evaluation of anti-vector measures. In addition, the gSG6 protein may represent a powerful model system to get a deeper understanding of molecular and cellular mechanisms underlying the immune tolerance and progressive desensitization to insect salivary allergens

Search for the production of dark matter in association with top-quark pairs in the single-lepton final state in proton-proton collisions at √s=8 TeV

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Search for vector-like T quarks decaying to top quarks and Higgs bosons in the all-hadronic channel using jet substructure

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Measurement of inclusive jet production and nuclear modifications in pPb collisions at root s(NN)=5.02 TeV

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