University of Khartoum

Humoral Immune response to P. falciparum antigens in population living in seasonal and unstable malaria transmission area (Eastern Sudan)

Humoral Immune response to P. falciparum antigens in population living in seasonal and unstable malaria transmission area (Eastern Sudan)

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Title: Humoral Immune response to P. falciparum antigens in population living in seasonal and unstable malaria transmission area (Eastern Sudan)
Author: Ibrahim, Gamila
Abstract: The attempts to eradicate malaria parasite with drug treatment or by control of the mosquito vector have shown no success. The progress in malaria vaccine development is an alternative hope for malaria control. The development of a vaccine, at least one that can limit the disease severity may be useful. Most of the the candidate vaccines produced are multi-component to overcome the problem of the complexity of the parasite life cycle and genetic diversity. They are based on the selection of parasite antigens that elicit protective immune response. This study was carried-out in Daraweesh village an area of unstable malaria transmission, Eastern Sudan. Individuals recruited for the study, are permanent residents of the village aged from 1-60 years. The study population consisted mainly of those individuals who developed clinical malaria (confirmed by microscopic diagnosis) or were PCR positive for P. falciparum malaria. Thirty one individuals (the cohort), were included in longitudinal study which was carried-out for two transmission seasons and also two long dry seasons (September 1996-April 1998). Blood samples (2-5ml) were collected, the first was taken before the initiation of the malaria treatment (day 0), and again 30 days after the initiation of the malaria treatment (day 30), then plasma samples were collected from individuals on monthly basis and were then continued up to April 1998. Sera and plasma of non-exposed donors from non-endemic area (Scotland) were used as negative controls, while sera from individuals from the same village (Daraweesh) having high antibodies level or showed a high clear positive antibody response to the different fragments of the merozoite surface proteins were used as positive control. In this study a panel of an immunologically well-characterized recombinant proteins, representing the conserved and polymorphic regions of the Merozoite Surface Antigens (MSP), in addition to Apical Membrane Antigen (AMA1) antigen of the Plasmodium falciparum, were used to investigate the natural acquisition of humoral immunity to malaria infection by individuals. For this study, thirty-two recombinant MSP proteins that have been expressed in Escherichia coli as GST fusions were used. The antigenicity of the different MSP and AMA1 antigen was assessed by Enzyme Linked Immunosorbant Assay (ELISA). The study showed that all the polymorphic and the conserved regions of MSP antigens and AMA1 were recognized by specific IgG antibodies. However, the overall frequency of antibody responses to all fragments was not the same. The antibody response to MSP fragments was significantly different between individuals, within each individual and even between variants. A persistant and continuous antibody responses were noticed among individuals, before the clinical malaria episode and continued over a period including the two transmission seasons and two long dry seasons, representative of these antigen fragments are: the C- terminal of MSP1 (MSP-119), the full-length of MSP2A and MSP2B, MSP2A T9 96 5/7 and AMA1 antigen. On the other hand other frragments of MSP antigens, MSP1(MSP1 BL2 and MSP1 BL4/5) and the polymorphic regions of MSP2A and MSP2B, showed low antibody response followed a documented clinical malaria infection. Short half life of antibody response was noticed in the polymorphic fragments of the MSP1(MSP1 BL2 and MSP1 BL4/5) and the polymorphic regions of MSP2A and MSP2B, the exception was the conserved C-terminal of MSP1 (MSP119), the full-length of MSP2A and MSP2B and MSP2A T996 5/7. The data presented in this thesis showed that, the C- terminal of MSP1 (MSP-119), the full-length of MSP2A and MSP2B, MSP2A T9 96 5/7 and AMA1 antigen are likely to be candidates in subunit vaccine.
URI: http://hdl.handle.net/123456789/7503
Date: 2015-03-25


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