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Immunity to malaria is slow to develop, is non-sterilising and wanes rapidly when immune adults migrate to non-endemic regions, suggesting that specific problems exist in the establishment and maintenance of functional long-lived immunological memory to malaria. Understanding the cellular and molecular basis of the inefficiency of immunity to malaria will greatly aid the search for effective vaccines, which together with antimalarial drugs and vector control, will be an essential component in the drive to eliminate malaria.
Whilst malaria-specific antibodies are associated with protection against parasites and disease symptoms, there is a debate around the longevity of antibody responses to malaria antigens with some reporting short-lived responses and others reporting long-lived responses. Additionally, observations from Kilifi, Kenya, and elsewhere suggest that malaria-specific antibody levels are greater in parasitised than in aparasitaemic individuals in spite of frequent exposure. This observation implies that malaria-specific antibody responses in children already exposed to malaria are short-lived, and has been confirmed in studies of the kinetics of responses to the P. falciparum parasite-induced erythrocyte surface antigens in children convalescing from acute infections. In these studies, short-lived antibody responses were associated with poor isotype-switching. Moreover, re-parasitisation of children during follow-up after the disease episode was not always associated with boosting of the initial antibody specificities. Subsequently, antibodies specific for several merozoite antigens were found to have shorter half-lives than normal.
Therefore, I am interested in determining the cellular and molecular deficits, if any, in the establishment of long-lasting malaria-specific antibody in humans.
Ndungu F.M., E.T. Cadman, J. Coulcher, E. Nduati, E. Couper, D.W. MacDonald, D. Ng, J. Langhorne (2009). "Functional Memory B Cells and Long-Lived Plasma Cells Are Generated after a Single Plasmodium chabaudi Infection in Mice." PLoS Pathog 5(12): e1000690. doi:10.1371/journal.ppat.1000690
Stephens, R., F. M. Ndungu, E. Cadman and J. Langhorne (2009). "Germinal Centre and Marginal Zone B cells expand quickly in a second Plasmodium chabaudi Malaria Infection Producing Mature Plasma cells." Parasite Immunol 31(1):20-31.
Langhorne, J., F. M. Ndungu, A. M. Sponaas and K. Marsh (2008). "Immunity to malaria: more questions than answers." Nat Immunol 9(7): 725-32.
Cadman, E. T., A. Y. Abdallah, C. Voisine, A. M. Sponaas, P. Corran, T. Lamb, D. Brown, F. Ndungu and J. Langhorne (2008). "Alterations of splenic architecture in malaria are induced independently of Toll-like receptors 2, 4, and 9 or MyD88 and may affect antibody affinity." Infect Immun 76(9): 3924-31.
Beeson, J. G., F. Ndungu, K. E. Persson, J. M. Chesson, G. L. Kelly, S. Uyoga, S. L. Hallamore, T. N. Williams, J. C. Reeder, G. V. Brown and K. Marsh (2007). "Antibodies among men and children to placental-binding Plasmodium falciparum-infected erythrocytes that express var2csa." Am J Trop Med Hyg 77(1): 22-8.
Ndungu, F. M., L. Sanni, B. Urban, R. Stephens, C. I. Newbold, K. Marsh and J. Langhorne (2006). "CD4 T cells from malaria-nonexposed individuals respond to the CD36-Binding Domain of Plasmodium falciparum erythrocyte membrane protein-1 via an MHC class II-TCR-independent pathway." J Immunol 176(9): 5504-12.
Urban, B. C. and F. M. Ndungu (2006). The role of dendritic cells in malaria. Handbook of Dendritic Cells. M. Lutz, N. Romani and A. Steinkasserer. Indianapolis, John Wiley & Sons Inc. 2: 651 - 658.
Ndungu, F. M., B. C. Urban, K. Marsh and J. Langhorne (2005). "Regulation of immune response by Plasmodium-infected red blood cells." Parasite Immunol 27(10-11): 373-84.
Dorfman, J. R., P. Bejon, F. M. Ndungu, J. Langhorne, M. M. Kortok, B. S. Lowe, T. W. Mwangi, T. N. Williams and K. Marsh (2005). "B cell memory to 3 Plasmodium falciparum blood-stage antigens in a malaria-endemic area." J Infect Dis 191(10): 1623-30.
Bull, P. C., A. Pain, F. M. Ndungu, S. M. Kinyanjui, D. J. Roberts, C. I. Newbold and K. Marsh (2005). "Plasmodium falciparum antigenic variation: relationships between in vivo selection, acquired antibody response, and disease severity." J Infect Dis 192(6): 1119-26.