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Genetic diversity and protective immunity to malaria infection and disease
1 September 2005 - 30 June 2015
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
DESCRIPTION (provided by applicant): Extreme genetic diversity in Plasmodium falciparum helps malaria parasites evade host immunity and impedes malaria vaccine development. Naturally acquired immunity to malaria is thought to represent the accumulation of protective immune responses to a repertoire of antigens and, importantly, to different variants of these antigens. But we remain largely ignorant of precisely which antigens and how many and which variants of these antigens must be recognized by which sorts of immune responses to afford natural or vaccine-induced protection. This project is largely focused on improving this understanding. Building on results of previous clinical translational research conducted in rural Mali, West Africa, we propose to further elucidate the mechanisms underlying both naturally acquired and vaccine-induced immune responses that protect against malaria infection and disease, and to use this knowledge to inform the development of broadly protective malaria vaccines. We will exploit recent technological advances to address at the genome-wide level questions that could previously be approached only one or a few genes at a time, developing new tools to assess immune responses against variant antigens and epitopes. In a prospective cohort study of children at risk for malaria infection and disease and in separate clinical trials of malaria vaccines, molecular and immunological correlates of natural and vaccine-induced protective immunity to P. falciparum infections and disease will be identified. This research is expected to provide information that will elucidate mechanisms underlying naturally acquired malaria immunity, improve the next generation of malaria vaccines and increase prospects for malaria elimination in Africa. RELEVANCE (See Instructions): Malaria parasites have evolved the ability to escape protective immune responses by varying the proteins that the immune system recognizes. This genetic diversity also makes it harder to develop a successful malaria vaccine. This project will study how changes in malaria genes and proteins relate to the risk of clinical malaria illness and to the ability of vaccines to prevent malaria. Study results are expected to provide information that will guide the development of effective malaria vaccines.
20 Resulting Publications
Amed Ouattara; Shannon Takala-Harrison; Mahamadou A Thera; Drissa Coulibaly; Amadou Niangaly; Renion Saye; Youssouf Tolo; Sheetij Dutta; D Gray Heppner; Lorraine Soisson; et al.The Journal of infectious diseases 2013;207(3):511-9.
Kavita Gandhi; Mahamadou A Thera; Drissa Coulibaly; Karim Traoré; Ando B Guindo; Ogobara K Doumbo; Shannon Takala-Harrison; Christopher V PloweThe American journal of tropical medicine and hygiene 2012;86(5):775-81.
Mahamadou A Thera; Christopher V PloweAnnual review of medicine 2012;63():345-57.
Mahamadou A Thera; Ogobara K Doumbo; Drissa Coulibaly; Matthew B Laurens; Amed Ouattara; Abdoulaye K Kone; Ando B Guindo; Karim Traore; Idrissa Traore; Bourema Kouriba; et al.The New England journal of medicine 2011;365(11):1004-13.
K E Lyke; M A Fernández-Viňa; K Cao; J Hollenbach; D Coulibaly; A K Kone; A Guindo; L A Burdett; R J Hartzman; A R Wahl; et al.Tissue antigens 2011;77(6):562-71.
Abdoul H Beavogui; Abdoulaye A Djimde; Aric Gregson; Abdoulaye M Toure; Adama Dao; Boubacar Coulibaly; Dinkorma Ouologuem; Bakary Fofana; Adama Sacko; Mamadou Tekete; et al.International journal for parasitology 2010;40(10):1213-20.
Mahamadou A Thera; Ogobara K Doumbo; Drissa Coulibaly; Matthew B Laurens; Abdoulaye K Kone; Ando B Guindo; Karim Traore; Mady Sissoko; Dapa A Diallo; Issa Diarra; et al.PloS one 2010;5(2):e9041.
Amed Ouattara; Jianbing Mu; Shannon Takala-Harrison; Renion Saye; Issaka Sagara; Alassane Dicko; Amadou Niangaly; Junhui Duan; Ruth D Ellis; Louis H Miller; et al.Malaria journal 2010;9():175.
Shannon L Takala; Drissa Coulibaly; Mahamadou A Thera; Adrian H Batchelor; Michael P Cummings; Ananias A Escalante; Amed Ouattara; Karim Traoré; Amadou Niangaly; Abdoulaye A Djimdé; et al.Science translational medicine 2009;1(2):2ra5.
S L Takala; C V PloweParasite immunology 2009;31(9):560-73.
Muminatou Jallow; Yik Ying Teo; Kerrin S Small; Kirk A Rockett; Panos Deloukas; Taane G Clark; Katja Kivinen; Kalifa A Bojang; David J Conway; Margaret Pinder; et al.Nature genetics 2009;41(6):657-65.
Kirsten E Lyke; Modibo Daou; Issa Diarra; Abdoulaye Kone; Bourema Kouriba; Mohamadou A Thera; Sheetij Dutta; David E Lanar; D Gray Heppner; Ogobara K Doumbo; et al.Vaccine 2009;27(15):2171-6.
Mahamadou A Thera; Ogobara K Doumbo; Drissa Coulibaly; Dapa A Diallo; Abdoulaye K Kone; Ando B Guindo; Karim Traore; Alassane Dicko; Issaka Sagara; Mahamadou S Sissoko; et al.PloS one 2008;3(1):e1465.
Shannon L Takala; David L Smith; Mahamadou A Thera; Drissa Coulibaly; Ogobara K Doumbo; Christopher V PloweThe American journal of tropical medicine and hygiene 2007;76(5):855-9.
Shannon L Takala; Drissa Coulibaly; Mahamadou A Thera; Alassane Dicko; David L Smith; Ando B Guindo; Abdoulaye K Kone; Karim Traore; Amed Ouattara; Abdoulaye A Djimde; et al.PLoS medicine 2007;4(3):e93.
Rosangela Salerno-Gonçalves; Marcelo B SzteinTrends in microbiology 2006;14(12):536-42.
Yacouba Cissoko; Modibo Daou; Kirsten E Lyke; Alassane Dicko; Issa Diarra; Abdoulaye Kone; Ando Guindo; Karim Traore; Gowdahalli Krishnegowda; Dapa A Diallo; et al.The American journal of tropical medicine and hygiene 2006;75(2):199-204.
Anne-Marie Deans; Kirsten E Lyke; Mahamadou A Thera; Christopher V Plowe; Abdoulaye Koné; Ogobara K Doumbo; Oscar Kai; Kevin Marsh; Margaret J Mackinnon; Ahmed Raza; et al.The American journal of tropical medicine and hygiene 2006;74(4):554-63.
Kirsten E Lyke; Alassane Dicko; Abdoulaye Dabo; Lansana Sangare; Abdoulaye Kone; Drissa Coulibaly; Ando Guindo; Karim Traore; Modibo Daou; Issa Diarra; et al.The American journal of tropical medicine and hygiene 2005;73(6):1124-30.
Mahamadou A Thera; Paul S Sehdev; Drissa Coulibaly; Karim Traore; Mamane N Garba; Yacouba Cissoko; Abdoulaye Kone; Ando Guindo; Alassane Dicko; Abdoul H Beavogui; et al.The Journal of infectious diseases 2005;192(10):1823-9.
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