The study aims at identifying protective immune response against severe malaria in young children. This study is based on our earlier studies of pregnancy malaria. Susceptibility to pregnancy malaria results from the unique binding phenotype of placental parasites that adhere to chondroitin sulfate A (CSA), a molecule that is expressed on the surface of the syncytiotrophoblast and appears throughout the intervillous spaces. Because CSA is not readily accessible for parasite adhesion in the nonpregnant host, women are nave to this parasite subpopulation before their first pregnancy, making first-time mothers most susceptible. Over successive pregnancies women develop specific humoral immunity to placental parasites in the form of anti-adhesion antibodies. Anti-adhesion antibodies are associated with reduced prevalence of infection, reduced parasite densities, and improved pregnancy outcomes. Based on these findings, in the current study we survey the binding phenotype of IE associated with discrete clinical syndromes collected from children participating in the immune-epi study at Ouelessebougou, Mali, and relate acquisition of anti-adhesion antibodies with protection from severe malaria. In addition to this activity, the Pregnancy Malaria Consortium identified several vaccine candidates, Recombinant forms of these candidates were used to immunize animals. The antibodies have been evaluated for their anti-adhesion activity of maternal parasites adapted to in-vitro culture. Currently we are evaluating the level of anti-adhesion activity using fresh isolate collected from pregnant women participating in the immune-epi studies at Ouelessebougou. These results will assist in the selection of pregnancy malaria vaccine targets.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2011
Total Cost
$157,719
Indirect Cost
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State
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Zip Code
Barry, Amadou; Issiaka, Djibrilla; Traore, Tiangoua et al. (2018) Optimal mode for delivery of seasonal malaria chemoprevention in Ouelessebougou, Mali: A cluster randomized trial. PLoS One 13:e0193296
Brickley, E B; Kabyemela, E; Kurtis, J D et al. (2017) Developing a novel risk prediction model for severe malarial anemia. Glob Health Epidemiol Genom 2:e14
Mahamar, Almahamoudou; Issiaka, Djibrilla; Barry, Amadou et al. (2017) Effect of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali. Malar J 16:289
Mahamar, Almahamoudou; Attaher, Oumar; Swihart, Bruce et al. (2017) Host factors that modify Plasmodium falciparum adhesion to endothelial receptors. Sci Rep 7:13872
Brickley, Elizabeth B; Spottiswoode, Natasha; Kabyemela, Edward et al. (2016) Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study. Am J Trop Med Hyg 95:817-826
Gonçalves, Bronner P; Prevots, D Rebecca; Kabyemela, Edward et al. (2016) Preparing for future efficacy trials of severe malaria vaccines. Vaccine 34:1865-7
Brickley, Elizabeth B; Wood, Angela M; Kabyemela, Edward et al. (2015) Fetal origins of malarial disease: cord blood cytokines as risk markers for pediatric severe malarial anemia. J Infect Dis 211:436-44
Raj, Dipak K; Nixon, Christian P; Nixon, Christina E et al. (2014) Antibodies to PfSEA-1 block parasite egress from RBCs and protect against malaria infection. Science 344:871-7
Gonçalves, Bronner P; Fried, Michal; Duffy, Patrick E (2014) Parasite burden and severity of malaria in Tanzanian children. N Engl J Med 371:482
Kabyemela, Edward; Gonçalves, Bronner P; Prevots, D Rebecca et al. (2013) Cytokine profiles at birth predict malaria severity during infancy. PLoS One 8:e77214

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