Mechanisms of naturally-acquired immunity to malaria

Objectives

The development of a highly effective malaria vaccine has been hindered in part by a poor understanding of the interaction between P. falciparum and the human immune system. Importantly, protective immunity to malaria can be acquired after repeated P. falciparum infections but wanes rapidly in the absence of ongoing exposure. The quality of the innate and adaptive immune responses that ultimately confers this protection and the mechanisms that underlie their inefficient acquisition and rapid loss are poorly understood. One of our objectives is to inform the discovery and development of new tools to prevent and treat malaria by addressing these critical knowledge gaps. To this end, we apply recent advances in immunology and genomics-based technology to rigorously conducted longitudinal cohort studies in malaria-endemic areas to deepen our understanding of the interaction between P. falciparum and the human immune system, to define molecular and cellular signatures of malaria immunity and to identify potential targets for malaria vaccines and monoclonal antibodies.

The five main objectives of this project are:
1) obtain high quality clinical data and biospecimens from ongoing longitudinal cohort studies in Mali in which exposure to P. falciparum infection and protection against malaria are reliably assessed;
2) determine the antigen specificity, function, kinetics and cellular basis of the antibody response to P. falciparum, including the isolation of monoclonal antibodies against various stages of the P. falciparum life cycle;
3) define the mechanisms by which P. falciparum-induced inflammation is regulated;
4) identify a molecular signature of immunity to malaria through systems biology approaches; and
5) determine the relationship between persistent asymptomatic P. falciparum infection and malaria risk, and elucidate the host and parasite factors that underlie this phenomenon.