Consortial Project 2

 

 

 

Started 2005

Consortial Project 2 studied the human genetic factors suspected to influence the antibody response to malaria parasite antigens, with a particular focus on antigens that are being strongly considered for vaccine development.

Objectives & Coordination

Genetic determinants of the immune response to malaria

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 reduces 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.

To better understand why people differ in their immune response to the parasite, and how this affects their level of resistance to the disease, we:

  • Worked with partner studies in a number of geographical locations to collected serum samples, DNA and epidemiological data from 17,000 people
  • Developed a standardised, scalable antibody-detection assay for known malarial antigens to allow an integrated analysis across study sites
  • Completed measurements of IgG antibody levels against the P. falciparum vaccine candidate antigens MSP1, MSP2, CSP and AMA1, and total IgE levels
  • Genotyped 200 single nucleotide polymorphisms (SNPs) across candidate genes and published malaria-associated SNPs

We then used the resulting data to investigate two basic questions:

  1. Across multiple study sites, do SNPs in immune response genes correlate with antimalarial antibody levels?
  2. Within individual sites, do both SNPs in immune response genes and antimalarial antibody levels correlate with key clinical phenotypic variables, for example disease severity?

Governance

This project began shortly after MalariaGEN was formed in 2005, and has greatly influenced our approach to collaborative science.

MalariaGEN Consortial Projects 1-4 are overseen by a Governance Committee.

The Publications and Presentations Committee (PPC) helps ensure that publications and presentations arising from our human consortial projects meet the criteria outlined in the Joint Policy of Data Sharing, Intellectual Property and Publications.

Sampling locations

  • Burkina Faso (BF)
  • Kenya (KE)
  • Mali (ML)
  • Senegal (SN)
  • Sri Lanka (LK)
  • Sudan (SD)
  • Tanzania (TZ)

Partner studies

Each partner study conducted epidemiological surveys to measure the immune response to malaria, in order to investigate any correlation between levels of infection and clinical illness.

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.

People

Investigators involved in Consortial Project 2 include:

Prof Abdoulaye Djimdé
Associate Professor of Parasitology and Mycology; Chief of the Molecular Epidemiology and Drug Resistance Unit
Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Mali
Wellcome Trust International Fellow
Malaria Programme, Wellcome Trust Sanger Institute, UK
Dr Adama Tall
Senior Epidemiologist
Institut Pasteur de Dakar, Senegal
Alioune Badara Ly
Senegalese Ministry of Health
Amagana Dolo
Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Mali
Anavaj Sakuntabhai
Institut Pasteur, Paris, France
Ayman Hussein
University of Khartoum, Sudan
MalariaGEN Affiliations
Projects
Dr Boubacar Maiga
Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Mali
Prof Deepika Fernando
Professor in Parasitology and Consultant Parasitologist
University of Colombo, Sri Lanka
Dr Deus Ishengoma
Researcher
National Institute for Medical Research (NIMR), United Republic of Tanzania
Researcher
East African Consortium for Clinical Research (EACCR), United Republic of Tanzania
Dr Edith Bougouma
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Burkina Faso
Hugh Reyburn
London School of Hygiene & Tropical Medicine, UK
Marita Troye-Blomberg
Wenner-Gren Institute, University of Stockholm, Sweden
Dr Martha Lemnge
Chief Research Scientist and Director of Tanga Research Centre
National Institute for Medical Research (NIMR), United Republic of Tanzania
Prof Muntaser Ibrahim
University of Khartoum, Sudan
Prof Nadira Karunaweera
Chair, Head of Department and Senior Professor of Parasitology
University of Colombo, Sri Lanka
Visiting Scientist
School of Public Health, Harvard University, USA
Dr Odile Puijalon
Emeritus Scientist
Institut Pasteur, Paris, France
Prof Ogobara Doumbo
Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Mali
Ousmane Boubacar Toure
Malaria Research and Training Centre, University of Science, Techniques and Technologies of Bamako, Mali
Patrick Corran
London School of Hygiene & Tropical Medicine, UK
Dr Rajika Dewasurendra
University of Colombo, Sri Lanka
Dr Sodiomon Bienvenu Sirima
Executive Director
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Burkina Faso
Scientific Team Leader
Groupe de Recherche Action en Sante (GRAS) Burkina Faso
Theonest Mutabingwa
Seattle Biomedical Research Institute, USA
Prof Tom Williams
Head of the Department of Epidemiology and Demography
KEMRI Wellcome Trust Research Programme, Kenya
Chair in Haemoglobinopathy Reseach
Imperial College London, UK