Genetic determinants of the immune response to malaria (CP2)
This consortial project seeks to discover human genetic factors that influence the antibody response to malaria parasite antigens, focusing particularly on antigens that are under strong consideration for vaccine development. Each partner study has conducted epidemiological surveys that attempt to correlate levels of infection and clinical illness with measurements of the immune response to malaria. The partner studies differ in their epidemiological study design and in the precise variables that are measured, but what all have in common is that they have provided samples of serum and DNA to a central repository. This allows all partner studies to share genetic data and anti-malarial antibody measurements made in a reference laboratory using a common set of laboratory protocols.
- Burkina Faso: The Centre National de Recherche et de Formation sur le Paludisme are completing longitudinal and cross-sectional surveys in 4 villages. Study>>
- Kenya: The KEMRI-Wellcome Reseach Programme is contributing samples from individuals under continous surveillance for malaria.
- Mali: The University of Bamako has two different CP2 study projects at Manteourou Study>> and Pongonon Study>>
- Tanzania: The Joint Malaria Programme, Kilimanjaro Christian Medical Centre recruited samples from cross-sectional surveys at two different altitudes. Study>>
- Tanzania: The National Institute for Medical Research recruited samples from eight villages in the Muheza district. Study>>
- Senegal: The Institut Pasteur de Dakar recruited samples from a long-term longitudinal study in two communities. Study>>
- Sri Lanka: The University of Colombo is following up on a cohort study with active case dectection carried out in 1992/3. Study>>
- Sudan:The University of Khartoum performed a continuous surveillance in two villages in an area of low malaria endemicity and transmission rates.
People living in malaria-endemic regions acquire some level of protective immunity against the disease as they get older. Although the immunity is only partial, it is important in reducing the amount of illness and death caused by malaria, and one of the main goals of vaccine developers is to achieve a similar level of immunity in young children. Unfortunately we still lack a good understanding of how protective immunity against malaria works, despite decades of scientific effort to dissect the molecular mechanisms. One aspect of the problem is to understand why people differ in their immune response to the parasite, and how this affects their level of resistance to the disease.
Across the different partner studies, we have collected serum samples, DNA and epidemiological data from 17,000 individuals. A key deliverable has been the development of a standardized, scalable antibody-detection assay for known malarial antigens, to allow an integrated analysis across study sites. Using this standardised method, we have recently completed measurements of IgG antibody levels against the P. falciparum vaccine candidate antigens MSP1, CSP and AMA1, plus total IgE levels.
Using these data we are now investigating on two basic questions. First, across multiple study sites, do SNPs in immune response genes correlate with anti-malarial antibody levels? Second, within individual sites, do both immune gene SNPs and anti-malarial antibody levels correlate with key clinical phenotypic variables, such as disease severity?