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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/11395

Title: Dynamics of immunological memory to plasmodium falciparum infection among Ghanaians living in a malaria hypo-endemic region
Authors: Sinclear, Caleb Kwame
Issue Date: 13-Sep-2018
Abstract: Plasmodium falciparum (Pf) malaria remains an important cause of morbidity and mortality in sub-Saharan Africa particularly among children under 5 years of age and pregnant women. In Ghana, malaria alone accounts for about 33% of all deaths in children under 5 years of age. Malaria deaths may be averted if an efficacious vaccine that can offer long-term protection against the disease was available. However, such a vaccine is currently non-existent primarily due to lack of understanding of the dynamics of immunological memory in P. falciparum infection. Protection offered by the world’s leading malaria vaccine candidate, RTS,S/AS01, showed an efficacy decline from 50% to 36% within a 4 year period, suggesting a waning immunological memory to drive an effective secondary immune response. B cells are the important custodians of immunological memory, capable of developing into antibody producing cells (plasma cells) to mount an immune response against invading pathogens. With a 1-year longitudinal design, sampling at 4 timepoints at quarterly intervals, the present study aimed to assess the immunological profiles of individuals living in the Greater Accra region of Ghana, a malaria endemic zone. The afro-immuno assay ELISA protocol was used to quantify antibody levels against candidate malaria vaccine antigens (AMA1, CSP, GLURP-R0 and R2, LSA1 and MSP3) and crude antigens of the schizonts stage parasite across the 4 sampling timepoints. A culture-based assay was used to determine memory B cell (MBC) responses against the whole parasite in the schizonts stage. A flow cytometry panel was also designed to profile the B cell phenotypes across the period of the study. The results showed transient changes in the antibody responses to the schizont extract antigen, the levels of memory B cell responses and mature B cell subsets over the study period. There was no significant difference in the antibody levels against all the 6 recombinant antigens across the timepoints. The present study speculates that the significant impact which was observed in the responses to the whole parasite antigen could be a result of a cumulative impact on thevii antibody levels against the other numerous antigens expressed in the schizont stage of the parasite that were not considered in this study. Although the parasite detection data did not provide supporting evidence to dynamics in transmission seasons, the transient changes observed in the MBC responses over the timepoints may be attributed to possible exhaustion of the MBCs at the known characteristic high transmission seasons of the year, as have been reported by other studies. Moreover, the study also observed an inverse relationship between the MBC subsets and the atypical B cells, although the design of the flow cytometric panel was not limited to malariaspecific B cell phenotypes. The present study concludes that the wane of immunological memory to P. falciparum is due to possible exhaustion of memory B cells into the ‘dysfunctional’ B cell type, atypical B cells, as have been speculated by previous studies.
Description: A thesis submitted to the Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology in partial fulfillment of the requirements for the degree of Master of Philosophy, 2017
URI: http://hdl.handle.net/123456789/11395
Appears in Collections:College of Science

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