Dynamics of immunological memory to plasmodium falciparum infection among Ghanaians living in a malaria hypo-endemic region
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Date
November, 2017
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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.