Malaria has become a major threat to children, pregnant women and the aging in Cameroon due to single and multiple drug resistance in Plasmodium falciparum malaria. New drugs, vector control measures and a malaria vaccine are a necessity. The need to characterize and understand the components of acquired immunity to malaria are urgent if we are to develop; a successful malaria vaccine that can be used in malaria endemic areas. Natural immunity to malaria does occur, albeit slowly, taking many years, and even then may not be complete. The slow development of immunity may be due to the differential and age-related responses to immunodominant, variant and conserved, subdominant P. falciparum immunologically relevant proteins. We and others have demonstrated that humoral and cellular responses to MSP-1, MSP-2, AMA-1, may be important for the induction of protective immunity. We hypothesize that children respond predominantly to immunodominant variant epitopes, leading to incomplete immunity, and older children and adults respond to conserved epitopes resulting in long term protective immunity. To test our hypotheses, we will examine over five years the cellular and humoral immune responses to these antigens in a rural study population including, infants ages 1-5 years, children in age groups of 6-10 and 10- 15 years, and adults aged 16-45 who are naturally exposed to malaria. We will also examine cellular immune responses to both conserved and variant epitopes from MSP-1, MSA-2, AND AMA-1 candidate vaccine antigens. The immune responses will be correlated with HLA type to determine whether HLA effects the specificity and/or rate of development of protective immunity. This study will be carried out through a unique partnership between researchers in the laboratory and in the field. Data provided on the immune status of the population may help identify those effector mechanisms required for protective immunity. Also, data from this study may help in the development of intervention strategies that will contribute to the control of malaria in Cameroon.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Georgetown University
United States
Zip Code
Chang, Sandra P; Kayatani, Alexander K K; Terrientes, Zilka I et al. (2010) Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4. Malar J 9:14
Thévenon, Audrey Davidson; Zhou, James A; Megnekou, Rosette et al. (2010) Elevated levels of soluble TNF receptors 1 and 2 correlate with Plasmodium falciparum parasitemia in pregnant women: potential markers for malaria-associated inflammation. J Immunol 185:7115-22
Taylor, Diane Wallace; Zhou, Aniong; Marsillio, Lauren E et al. (2004) Antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A and to the C terminus of merozoite surface protein 1 correlate with reduced placental malaria in Cameroonian women. Infect Immun 72:1603-7
Johnson, Armead H; Leke, Rose G F; Mendell, Nancy R et al. (2004) Human leukocyte antigen class II alleles influence levels of antibodies to the Plasmodium falciparum asexual-stage apical membrane antigen 1 but not to merozoite surface antigen 2 and merozoite surface protein 1. Infect Immun 72:2762-71
Xi, Guoling; Leke, Rose G F; Thuita, Lucy W et al. (2003) Congenital exposure to Plasmodium falciparum antigens: prevalence and antigenic specificity of in utero-produced antimalarial immunoglobulin M antibodies. Infect Immun 71:1242-6
Zhou, Ainong; Megnekou, Rosette; Leke, Robert et al. (2002) Prevalence of Plasmodium falciparum infection in pregnant Cameroonian women. Am J Trop Med Hyg 67:566-70
Staalsoe, T; Megnekou, R; Fievet, N et al. (2001) Acquisition and decay of antibodies to pregnancy-associated variant antigens on the surface of Plasmodium falciparum-infected erythrocytes that protect against placental parasitemia. J Infect Dis 184:618-26
O'Neil-Dunne, I; Achur, R N; Agbor-Enoh, S T et al. (2001) Gravidity-dependent production of antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate proteoglycan during pregnancy. Infect Immun 69:7487-92
Johnson, A; Leke, R; Harun, L et al. (2000) Interaction of HLA and age on levels of antibody to Plasmodium falciparum rhoptry-associated proteins 1 and 2. Infect Immun 68:2231-6
Ellis, J M; Mack, S J; Leke, R F et al. (2000) Diversity is demonstrated in class I HLA-A and HLA-B alleles in Cameroon, Africa: description of HLA-A*03012, *2612, *3006 and HLA-B*1403, *4016, *4703. Tissue Antigens 56:291-302

Showing the most recent 10 out of 11 publications