Malaria caused by P. vivax is responsible for substantial morbidity in many developing countries and is the major cause of clinical malaria outside of Africa.  Vivax malaria severely incapacitates infected persons of all ages.  It leads to 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 (DARC) are infected with blood-stage P. vivax.  Parasite recognition of this erythrocyte surface receptor is dependent upon the Duffy binding protein (DBP) region II (DBPII), the ligand domain, making DBP an ideal vaccine candidate. However the major obstacle for developing DBP as a vaccine is that natural immunity is biased towards strain-specific polymorphic DBPII residues that change antigenic character as a mechanism of immune evasion.  The goal of our project is to overcome this obstacle by using advanced analytical tools to facilitate development of an anti-vivax vaccine capable of eliciting a strain-transcending antibody inhibition of parasite development. These studies were initiated as part of NIH grant R01 AI033656 and are currently funded by a 5-year NIH grant R01AI064478-01 (2006-2011).

Selected Publications: Duffy Binding Protein related Publications

Adams JH, Hudson DE, Torii M, Ward GE, Wellems TE, Aikawa M, Miller LH. (1990). The Duffy receptor family is located within the micronemes of invasive malaria merozoites. Cell. 63:141-153.

Adams JH, Sim BKL, Dolan SA, Fang X, Kaslow DC, Miller LH.  (1992). A family of erythrocyte binding proteins in malaria parasites.  Proceedings of the National Academy of Sciences (USA). 89: 7085-7089.

Ohas EA, Adams JH, Waitumbi JN, Orago ASS, Barbosa A, Lanar DE, Stoute JA. (2004). Measurement of antibody levels against region II of the erythrocyte binding antigen 175 (EBA-175) of Plasmodium falciparum in a malaria holoendemic area of western Kenya. Infection and Immunity. 72: 725-741.

VanBuskirk KM, Cole-Tobian JL, Sevova E., Baisor M, Bockarie M, King CL, Adams JH. (2004). Antigenic drift in the ligand domain of Plasmodium vivax Duffy binding protein confers resistance to inhibitory antibodies. Journal of Infectious Diseases. 190: 1556-1562.

VanBuskirk KM, Sevova E., Adams JH. (2004). Mutation analysis identifies functionally important residues in the ligand domain of the Plasmodium vivax Duffy binding protein. Proceedings of the National Academy of Sciences (USA). 101: 15754-15759.

Chattopadhyay D, Rayner JC, McHenry AM, Adams JH. (2006). (Invited review) The three dimensional structure of Plasmodium falciparum EBA175 ligand domain provides insight into the molecular basis of host specificity. Trends in Parasitology. 22: 143-145.

McHenry AM, Adams JH. (2006). (Invited review). The crystal structure of Plasmodium knowlesi DBPa DBL domain and its implications for immune evasion. Trends in Biochemical Sciences. 31: 487-491.