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?

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

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 differed in their epidemiological study design and in the precise variables that are measured, but what all had in common is that they have provided samples of serum and DNA to a central repository. This allowed 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:

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 Edith Bougouma

Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Burkina Faso

Hugh Reyburn

London School of Hygiene & Tropical Medicine, UK

Prof Kevin Marsh

Professor of Tropical Medicine
Nuffield Department of Medicine, University of Oxford, UK
KEMRI Wellcome Trust Research Programme, Kenya

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

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 Research
Imperial College London, UK