Dissecting the antibody response to Plasmodium falciparum-infected erythrocytes (360G-Wellcome-204689_Z_16_Z)

The antibody response against Plasmodium falciparum-infected erythrocytes (IEs) has been associated with protection against malaria, but the characteristics of this response at the monoclonal antibody level remain an open question. We have recently developed a high-throughput platform to isolate monoclonal antibodies against IEs that allowed us to identify novel LAIR1-containing antibodies that target RIFINs on the IE surface (Tan et al. 2016, Nature). Here, we propose to use this technology to interrogate the immune response of well-characterized malaria-exposed Malian individuals against IEs at the monoclonal antibody level. We plan to: a) compare the responses of naturally protected and non-protected individuals to identify potential signatures of protection, b) isolate antibodies that broadly target late-stage IEs and identify novel conserved antigens as malaria vaccine candidates, and c) study the repertoire of LAIR1-containing antibodies in Malian individuals. We believe that this plan is feasible, as we have obtained preliminary data suggesting that several Malian plasma recognize the majority of late-stage IEs and that a sizable proportion (5-10%) of these individuals possess LAIR1-containing antibodies. From this work, we hope to identify aspects of the antibody response that protect malaria-exposed individuals, potentially including broadly reactive antibodies against conserved IE antigens.