Kirsten E Lyke

Grant Detail

The grant detail shows the name of the PI, active dates of the project, the funding institute and the abstract of the grant. This abstract is what is used to create the fingerprint of the grant. If any publications referencing this grant are found in the data, they will be listed here as well.

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

• 1.

  2013

  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.

  Molecular basis of allele-specific efficacy of a blood-stage malaria vaccine: vaccine development implications.

  The Journal of infectious diseases 2013;207(3):511-9.

• 2.

  2012

  Kavita Gandhi; Mahamadou A Thera; Drissa Coulibaly; Karim Traoré; Ando B Guindo; Ogobara K Doumbo; Shannon Takala-Harrison; Christopher V Plowe

  Next generation sequencing to detect variation in the Plasmodium falciparum circumsporozoite protein.

  The American journal of tropical medicine and hygiene 2012;86(5):775-81.

• 3.

  2012

  Mahamadou A Thera; Christopher V Plowe

  Vaccines for malaria: how close are we?

  Annual review of medicine 2012;63():345-57.

• 4.

  2011

  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.

  A field trial to assess a blood-stage malaria vaccine.

  The New England journal of medicine 2011;365(11):1004-13.

• 5.

  2011

  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.

  Association of HLA alleles with Plasmodium falciparum severity in Malian children.

  Tissue antigens 2011;77(6):562-71.

• 6.

  2010

  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.

  Low infectivity of Plasmodium falciparum gametocytes to Anopheles gambiae following treatment with sulfadoxine-pyrimethamine in Mali.

  International journal for parasitology 2010;40(10):1213-20.

• 7.

  2010

  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.

  Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.

  PloS one 2010;5(2):e9041.

• 8.

  2010

  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.

  Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine.

  Malaria journal 2010;9():175.

• 9.

  2009

  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.

  Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development.

  Science translational medicine 2009;1(2):2ra5.

• 10.

  2009

  S L Takala; C V Plowe

  Genetic diversity and malaria vaccine design, testing and efficacy: preventing and overcoming 'vaccine resistant malaria'.

  Parasite immunology 2009;31(9):560-73.

• 11.

  2009

  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.

  Genome-wide and fine-resolution association analysis of malaria in West Africa.

  Nature genetics 2009;41(6):657-65.

• 12.

  2009

  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.

  Cell-mediated immunity elicited by the blood stage malaria vaccine apical membrane antigen 1 in Malian adults: results of a Phase I randomized trial.

  Vaccine 2009;27(15):2171-6.

• 13.

  2008

  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.

  Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

  PloS one 2008;3(1):e1465.

• 14.

  2007

  Shannon L Takala; David L Smith; Mahamadou A Thera; Drissa Coulibaly; Ogobara K Doumbo; Christopher V Plowe

  Short report: rare Plasmodium falciparum merozoite surface protein 1 19-kda (msp-1(19)) haplotypes identified in Mali using high-throughput genotyping methods.

  The American journal of tropical medicine and hygiene 2007;76(5):855-9.

• 15.

  2007

  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.

  Dynamics of polymorphism in a malaria vaccine antigen at a vaccine-testing site in Mali.

  PLoS medicine 2007;4(3):e93.

• 16.

  2006

  Rosangela Salerno-Gonçalves; Marcelo B Sztein

  Cell-mediated immunity and the challenges for vaccine development.

  Trends in microbiology 2006;14(12):536-42.

• 17.

  2006

  Yacouba Cissoko; Modibo Daou; Kirsten E Lyke; Alassane Dicko; Issa Diarra; Abdoulaye Kone; Ando Guindo; Karim Traore; Gowdahalli Krishnegowda; Dapa A Diallo; et al.

  Serum antibody levels to glycosylphosphatidylinositols in specimens derived from matched Malian children with severe or uncomplicated Plasmodium falciparum malaria and healthy controls.

  The American journal of tropical medicine and hygiene 2006;75(2):199-204.

• 18.

  2006

  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.

  Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red blood cell selectivity with malaria virulence.

  The American journal of tropical medicine and hygiene 2006;74(4):554-63.

• 19.

  2005

  Kirsten E Lyke; Alassane Dicko; Abdoulaye Dabo; Lansana Sangare; Abdoulaye Kone; Drissa Coulibaly; Ando Guindo; Karim Traore; Modibo Daou; Issa Diarra; et al.

  Association of Schistosoma haematobium infection with protection against acute Plasmodium falciparum malaria in Malian children.

  The American journal of tropical medicine and hygiene 2005;73(6):1124-30.

• 20.

  2005

  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.

  Impact of trimethoprim-sulfamethoxazole prophylaxis on falciparum malaria infection and disease.

  The Journal of infectious diseases 2005;192(10):1823-9.

Scientific Context

This section shows information that has been computed by using the fingerprint of the grant, including related publications, related experts and related grants - all with fingerprints representing significant amounts of overlap between their fingerprint and this grant. The red dots indicate whether those experts or terms actually appear within this grant, showing potential and actual connections.