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The Project

Title : Functional Immuno-genetic Correlates
           of Immunity to Malaria

This project will define immune-genetic correlates of malaria immunity and strengthen research capacity through: 1. Identification of immuno-genetic determinants of immunity to malaria: Malaria immunity has been associated with antibody titres and infection outcome often ignoring polymorphisms in host genes crucial for antibody function. Here, interactions between polymorphisms in (ITGB2, FCGR2A, FCGR2B, FCGR3A, FCGR3B, IGHG3) genes, quality and quantity of malarial antibodies in relation to risk of malaria will be assessed. 2. Dynamics of Plasmodium falciparum (Pf) genetic variations underlying acquisition of immunity to malaria: The high variability of Pf infection outcome is inadequately explained by host related factors alone. Here, sequences and expression profiles of genes encoding proteins crucial for parasite invasion, transmission and cytoadherence will be evaluated from parasite strains during one malaria season. 3. Functional assessment of naturally acquired malarial antibodies: Growth Inhibition Assay (GIA), Antibody Dependent Cellular Inhibition (ADCI) and Antibody Dependent Respiratory Burst (ADRB) assays will be established. Genetic and phenotypic factors for effector cell function in ADCI and ADRB will be ascertained. 4. Functional assessment of vaccine boosted malarial antibodies: GMZ2 Phase 2b trial samples will be assessed for functional antibodies by the GIA, ADCI and ADRB assays. Polymorphisms in relevant host genes will be assessed. Statistical models for analyzing preclinical and clinical data incorporating host and parasite genetic factors will be proposed.

 

Objectives

The overall goal of the project is to build human and Institutional capacity in the conduct of sustainable cutting edge malaria vaccine related research that will improve the general well-being of populations living in malaria endemic areas. The partners include Noguchi Memorial Institute for Medical Research (NMIMR), Kintampo Health Research Centre (KHRC), Navrongo Health Research Centre (NHRC) in Ghana and Statens Serum Institut (SSI), Københavns Universitet (KU) in Denmark


The project's specific objectives correspond to five work packages (WP), each having specific measurable outputs that translate into stronger health research capacity building as follows:

1. Conducting of a longitudinal cohort study (LCS) in Danfa and Pantang, which are two sub-districts of the La-Nkwantanang Madina Municipality, a high malaria endemic region in Ghana and using an ongoing blood draw protocol to optimize ADCI and GIA bioassays - WP1. This WP will ensure the availability of optimized bioassays and biological samples with accompanied morbidity data for the execution of WP2-6.

2. Assessment of antibody functionality in individuals naturally exposed to Pf and the interaction between antibodies and host genetic factors in relation to the risk of clinical malaria- WP2

3. Assessment of the dynamics of Pf genetic variations that underlie the acquisition of immunity to malaria – WP3

4. Statistical modeling of age-specific risk of malaria and relative contributions of host, parasite and environmental associated factors to the risk of malaria – WP4

5. Assessment of antibody functionality in GMZ2 immunized individuals and the interaction between GMZ2 induced antibodies and host genetic factors in relation to the risk of malaria – WP5

6. Evaluation of the anti-parasite activity of naturally acquired (LCS) and vaccine (GMZ2) induced IgG in the context of host genetic factors using ADRB – WP6




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