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Induction and maintenance of Immunological memory to Human Malaria


Malaria remains a significant threat to human health. The development of an effective malaria vaccine is a major global health priority, but despite intensive malaria research, a malaria vaccine remains elusive. A detailed understanding of the mechanisms involved in the induction and maintenance of human immune responses to malaria is fundamental for the rational design of vaccines. The aim of this proposal is to characterise the induction and maintenance of B and T cell responses to Plasmodium falciparum in defined human populations: first, malaria-exposed individuals living in London, and second, immune, semi-immune and non-immune adults, classified according to their level of exposure to malaria, in North-eastern Tanzania.

Specifically, this proposal aims to:
1) characterise memory B and T cell responses to Plasmodium following parasite infection;
2) describe the kinetics and duration of B and T cell memory responses to Plasmodium in individuals with single or multiple, fully documented, malaria infection s; and
3) compare and contrast B and T cell responses to Plasmodium in cohorts of individuals with varying degrees of acquired immunity.

Analyses of precursor frequencies, phenotypic and functional characteristics of memory B and T cell responses to crude malaria antigens and leading vaccine antigens (circumsporozoite protein, merozoite surface proteins-1 and -2, and apical membrane antigen-1) will be performed. To our knowledge, this is the most comprehensive study of memory cell responses to malaria that has been attempted in a field setting and will generate entirely novel data relating to the longevity and stability of immunological memory to malaria at the cellular level. Furthermore, detailed characterisation of the different aspects of anti-malaria immune responses will lead to identification of in vitro correlates of protection that should be most useful in monitoring current and future vaccine candidates.

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