Longitudinal analyses of immune responses to Plasmodium falciparum derived peptides corresponding to novel blood stage antigens in coastal Kenya.

We have recently described 95 predicted alpha-helical coiled-coil peptides derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy peptides recognized with the highest level of prevalence by sera from three endemic areas were selected for further studies. In this study, we sequentially examined antibody responses to these synthetic peptides in two cohorts of children at risk of clinical malaria in Kilifi district in coastal Kenya, in order to characterize the level of peptide recognition by age, and the role of anti-peptide antibodies in protection from clinical malaria. Antibody levels from 268 children in the first cohort (Chonyi) were assayed against 70 peptides. Thirty-nine peptides were selected for further study in a second cohort (Junju). The rationale for the second cohort was to confirm those peptides identified as protective in the first cohort. The Junju cohort comprised of children aged 1-6 years old (inclusive). Children were actively followed up to identify episodes of febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed significantly (p<0.05) increased antibody recognition in older children and 40 showed significantly increased antibody recognition in parasitaemic children. Ten peptides were associated with a significantly reduced odds ratio (OR) for an episode of clinical malaria in the first cohort of children and two of these peptides (LR146 and AS202.11) were associated with a significantly reduced OR in both cohorts. LR146 is derived from hypothetical protein PFB0145c in PlasmoDB. Previous work has identified this protein as a target of antibodies effective in antibody dependent cellular inhibition (ADCI). The current study substantiates further the potential of protein PFB0145c and also identifies protein PF11_0424 as another likely target of protective antibodies against P. falciparum malaria

Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif

To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens

Don't you know that you want to trust me? Subliminal goal priming and persuasion

International audienceWe investigated the effect of goal priming on the processing of a persuasive message. Before reading a persuasive message about tap water consumption, participants were subliminally primed (or not) with the goal “to trust”. Subsequently, they completed a questionnaire about their perception of the message, the source of the message, and tap water consumption intentions. The results indicated that non-consciousactivation of the goal “to trust” leads to a better evaluation of the message, increases behavioral intentions in accordance with the message, and positively influences the assessment of the source

Modeling Culicoides abundance in mainland France: implications for surveillance

International audienceBackground Biting midges of the genus Culicoides Latreille (Diptera: Ceratopogonidae) are involved in the transmission of several viruses affecting humans and livestock, particularly bluetongue (BTV). Over the last decade, Culicoides surveillance has been conducted discontinuously and at various temporal and spatial scales in mainland France following the BTV epizootics in 2008-2009 and its reemergence and continuous circulation since 2015. The ability to predict seasonal dynamics and spatial abundance of Culicoides spp. is a key element in identifying periods and areas at high risk of transmission in order to strengthen surveillance for early detection and to establish seasonally disease-free zones. The objective of this study was to model the abundance of Culicoides spp. using surveillance data. Methods A mixed-effect Poisson model, adjusted for overdispersion and taking into account temperature data at each trap location, was used to model the weekly relative abundance of Culicoides spp. over a year in 24 vector zones, based on surveillance data collected during 2009-2012. Vector zones are the spatial units used for Culicoides surveillance since 2016 in mainland France. Results The curves of the predicted annual abundance of Culicoides spp. in vector zones showed three different shapes: unimodal, bimodal or plateau, reflecting the temporal variability of the observed counts between zones. For each vector zone, the model enabled to identify periods of vector activity ranging from 25 to 51 weeks. Conclusions Although the data were collected for surveillance purposes, our modeling approach integrating vector data with daily temperatures, which are known to be major drivers of Culicoides spp. activity, provided areas-specific predictions of Culicoides spp. abundance. Our findings provide decisions makers with essential information to identify risk periods in each vector zone and guide the allocation of resources for surveillance and control. Knowledge of Culicoides spp. dynamics is also of primary importance for modeling the risk of establishment and spread of midge-borne diseases in mainland France

Evaluation of the cost-effectiveness of the bovine brucellosis surveillance-control system in France through epidemiological modelling

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Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.

A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal