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Students

Caleb Sinclear
Mphil Candidate
Project Title
Dynamics of immunological memory in Plasmodium falciparum infection
 
Executive Summary

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 1. In Ghana, malaria alone accounts for about 33% of all deaths in children under 5 years of age 2. 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 Pf infection. Currently, protection afforded by the world’s leading malaria vaccine candidate, the RTS,S/AS01, declines from 50% to 36% efficacy within a 4 year period 3 suggesting a waning immunological memory to drive an effective secondary immune response. B cells are the primary custodians of immunological memory capable of developing into antibody producing cells (plasma cells) to mount an immune response against invading pathogens, however, the impact Pf infection on their activity remains unclear. Others have proposed that the slow acquisition of protective immunity to malaria may be due to Pf induced accumulation of atypical memory B cells 4 with similar phenotypic characteristics to the functionally “exhausted” B cells found in HIV-patients 5. However, a direct association between Pf exposure, atypical memory B cells, and acquisition of protective immunity remains to be shown 6. It is also yet to be shown if immunological memory to antigens expressed in different stages of Pf life cycle are acquired and maintained in a similar manner. The current study will therefore use a 2 year longitudinal clinical, parasitological, antigen specific antibody and B cell frequency as well as B cell immuno-phenotyping data to elucidate the dynamics of immunological memory in Plasmodium falciparum infection.

 
 Objective

To assess the acquisition and profiles of immunological memory to malaria in individuals living in an endemic population.

  • To measure and compare B cell responses against Pf specific antigens (AMA1, GLURP, MSP3, CSP, PfEMP1-HB3VAR06 and -IT4VAR60) in naturally exposed individuals.
  • To assess the profile of B cell subpopulations in relation to Pf infection across different transmission seasons
  • To evaluate the relationship between malaria specific B cell subpopulations and IgG antibodies against specific Pf antigens (AMA1, GLURP, MSP3, CSP, PfEMP1-HB3VAR06 and -IT4VAR60).




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