Identifying functional antibody responses that protect against malaria in children, version 1.0
| dc.contributor.author | Rogerson, Stephen | |
| dc.contributor.author | Seydel, Karl | |
| dc.date.accessioned | 2022-09-13T09:11:28Z | |
| dc.date.available | 2022-09-13T09:11:28Z | |
| dc.date.issued | 2022-08-03 | |
| dc.description | Observational cohort study | en_US |
| dc.description.abstract | Type of study: Observational cohort study The Problem: Although antibodies have been shown to be important for the protection against malarial disease, the specific characteristics of these protective antibodies have not been well delineated. Methodology: The study population of interest will be children aged 1-8 years of age drawn from three ongoing COMREC-approved studies. This is a secondary analysis of samples already being collected from three ongoing COMREC-approved studies. Children in the ongoing “Treatment of brain swelling in pediatric cerebral malaria” study (P. 09/16/2024, PI: Taylor) with cerebral malaria will be matched with children with uncomplicated malaria from the study “Characterization of Plasmodium falciparum var/PfEMP1 type and immune response to PfEMP1 in severe and uncomplicated clinical malaria” (P.01/15/1668, PI:Kim) and children with asymptomatic parasitemia from the “Malaria pathogenesis: Progression cohort and extremes, case control study” (P.11/18/2530, PI: Seydel). Children with no evidence of malaria infection in the “Malaria pathogenesis” study will be used as uninfected controls. After obtaining informed consent from their primary caretaker, a brief medical history and demographic information will be collected from all participants. Children with cerebral malaria are having a 10ml blood sample collected. Children in the uncomplicated and asymptomatic cohorts are having 4mls of blood collected. Plasma from this sample, as well as peripheral blood mononuclear cells from these samples will be purposed for this proposed study. No additional blood will be drawn for the purpose of this study. The serum from these studies will first be used in a Luminex assay to determine the strongest candidates that might be leading to protective immunity. Antibody and PBMC responses to these antigens will then be prioritized in the subsequent assays. These assays will involve the functional and biochemical characterization of antibodies in ~50 ways (see Research Strategy below). Comparison groups will be among the three disease severity types as well as between acute and convalescent sera. Data from these assays will be analyzed using elastic net regularized logistic regression and partial least squares discriminant analysis to identify the antibody characteristics associated with disease severity. Broad Objective: To identify the biophysical and functional characteristics of antibodies that protect against clinical malaria in children. Specific Objectives: 1) To use the Luminex bead approach to identify a subset of five P. falciparum expressed proteins that serve as targets of protection against cerebral malaria. To use the Systems Serology approach to identify biophysical and functional characteristics of antibodies against the targets identified in Aim 1, that either protect from cerebral malaria or develop during convalescence from cerebral malaria. 3) To use the Systems Serology approach to identify the biophysical and functional characteristics of antibodies that are present in children with asymptomatic P. falciparum infection and not in children with clinical disease. Expected Findings: We expect to find a subset of PfEMP1 domains, as well as a subset of proteins expressed on the merozoite stage of the parasite, that are most important in the protection of children from severe malaria. We also expect to find a distinct antibody profile that is most effective at controlling the P. falciparum infection. This will be accomplished by comparing the antibody characteristics seen in children with severe disease to those seen in children with milder infection, and (for the second question) comparing antibody responses in children with asymptomatic parasite infection to children with symptomatic malaria. Dissemination: Results will be disseminated to the medical community through peerreviewed publications and presentations at relevant scientific conferences. Results will also be shared with KUHeS at the annual Research Dissemination Conference. Annually, we will also be providing COMREC updates as required in the annual report. | en_US |
| dc.description.sponsorship | NIH | en_US |
| dc.identifier.uri | http://rscarchive.kuhes.ac.mw/handle/20.500.12988/1086 | |
| dc.language.iso | en | en_US |
| dc.publisher | Kamuzu University of Health Sciences | en_US |
| dc.relation.ispartofseries | Protocol;P.05/22/3634 | |
| dc.title | Identifying functional antibody responses that protect against malaria in children, version 1.0 | en_US |
| dc.type | Plan or blueprint | en_US |