Duffy Pathogenesis & Immunity Research Group

The Pathogenesis and Immunity Section of LMIV conducts human and animal studies of malaria pathogenesis and host immunity, including population-based studies in communities exposed to Plasmodium falciparum. Our research emphasizes pregnant women and children, the populations most susceptible to malaria morbidity and mortality, with collaborative cohort studies ongoing in Mali, Liberia and Guinea. We employ a suite of tools including transcriptomics, antibody repertoire analysis, and multiparameter flow cytometry to interrogate host responses involved in disease and protective immunity.

Our over-arching goal is to conceive novel malaria vaccine concepts and to discover target antigens of protective immunity. Our group first described the distinct P. falciparum phenotype that causes placental malaria, and the findings have guided the design of a vaccine being developed at LMIV to protect pregnant women from malaria. Together with the Kurtis group at Brown University, we have identified target antigens of blood stage malaria antibodies that mediate protection from severe malaria through novel mechanisms, such as parasite programmed cell death. In addition to our studies of blood-stage parasites, we have a collaborative program to study liver-stage malaria parasites, which are the target for vaccines that can completely prevent human infection. Using transcriptomic approaches, we have identified novel liver stage parasite antigens that enhance sterile immunity when used in combination vaccines and tested in preclinical models of malaria.

Scientists from our section collaborate closely with the LMIV Vaccine Development Unit to characterize the molecular immune response to vaccine candidates tested in humans, and to understand mechanisms of protective immunity conferred by whole malaria organism vaccines. As part of these studies, we recently generated the first human monoclonal antibodies against P. falciparum gametes and revealed the corresponding parasite epitopes that mediate transmission blocking vaccine activity. We have also identified a novel role for Vδ2 T cells in the induction of protective CD8 resident memory T cells that kill parasites during liver stage development.