Malaria caused by Plasmodium vivax is responsible for substantial morbidity in developing countries, producing 75-90 million cases of clinical malaria each year. Increasing prevalence of drug resistance in P. vivax, its global distribution and the appearance of more virulent forms of vivax malaria emphasizes the need for development of vaccines against this disease. Vivax malaria severely incapacitates infected persons, causing severe anemia, especially in young children, and an increased risk of low-birth-weight babies in pregnant women. Immunity to erythrocyte invasion ligands plays the critical role in controlling the blood-stage infection of P. vivax, since this malaria parasite does not sequester. Only persons that express the Duffy blood group antigen are infected with blood-stage P. vivax. Recognition of this human erythrocyte surface receptor is dependent upon the Duffy binding protein (DBP) cysteine-rich ligand domain, also known as region II or Duffy binding-like (DBL) domain. This essential interaction is a critical weakness in the parasite's life cycle. The major obstacle for developing this antigen as an effective vaccine is its high degree of polymorphism that makes ineffective the normal immune response following infection. Understanding the DBP-DARC interaction provides a model for all erythrocytes binding domains for Plasmodium-erythrocyte interaction.
The specific aims will define the immunological and functional properties of the DBP ligand domain and identify functionally conserved determinants of the receptor-binding site that are able to induce a broadly inhibitory antibody response capable of inhibiting blood-stage development of Plasmodium vivax.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI064478-05
Application #
7673394
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
MO, Annie X Y
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$679,373
Indirect Cost
Name
University of South Florida
Department
Other Health Professions
Type
Schools of Public Health
DUNS #
069687242
City
Tampa
State
FL
Country
United States
Zip Code
33612
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