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.
Midterm report 2016:
The prevalence of asymptomatic malaria parasitaemia among children (aged 0.5-12 yrs) in the study community was 7% during the dry season. All clinical and asymptomatic microscopic slides have been read once and are currently being double-read by a second microscopist. The final data should be available by August 2017. Similarly, weekly follow up data are still being entered into the database by two data entry clerks simultaneously.
This double entry is to allow for quality control. Discrepancies will be resolved by a third entry by a different clerk. Currently, a two color flow cytometry readout for the parasite growth inhibition assay has now been optimized at the NMIMR. Opsonic phagocytosis, immunofluorescence and multiplex (containing 21 malaria antigens) assay antibody data on GMZ2 clinical trial samples from Burkina Faso (n=540) and Navrongo (150) have been generated and are being analysed. Also, ELISA antibody data on 7 malaria antigens havebeen generated on the longitudinal cohort (n=996) samples pending analysis.The study was presented to the NMIMR research community during an Institutional seminar which also allowed us to solicit for volunteers for the blood draw protocol. The entire study was also presented at the Immunology Department of NMIMR at the weekly Journal club. In addition to presenting the study to the medical team and staff at the Danfa Health Centre (DHC) where the study was carried out, we also held a grand durbar which was attended by the Chief of Danfa, the municipal health director for the study area, the Assembly Man of the area, over 450 community members and staff of the DHC. The study objectives were explained to all in the local popular Ghanaian languages spoken in the community and there was an open forum for questions from the community members to be addressed. Since the commencement of their programs, each student has presented their synopsis and update reports at journal clubs and their respective universities. One manuscript has been published with several in preparation and the PhD Biostatistics student has defended his thesis in public.