Structure and interactions of the malarial surface antigen AMA1 [ 2001 - 2003 ]

Research Grant

Researchers: Prof Raymond Norton (Principal investigator) ,  A/Pr Michael Foley ,  Robin Anders

Brief description Malaria remains one of the most serious infectious diseases in the world today, being responsible for 1-2 million deaths annually. There is an urgent need for a vaccine against this disease, particularly because of the recent increase in forms of the parasite resistant to many of the best anti-malarial drugs. A clearer understanding of the structure of antigens in the parasite that induce a protective response in infected individuals would provide a stimulus to research into recombinant antigens as vaccines and a deeper understanding of the host-parasite interaction. AMA1 is an asexual stage antigen and a leading vaccine candidate. Little is known about the function of this protein, but it has been proposed to play a role in invasion of red blood cells. The specific aims of this project are to determine the three-dimensional structures of the three major structural domains of AMA1 and of the complete AMA1 ectodomain. The interaction of one or more of these domains with Fab fragments of protective antibodies raised against intact AMA1 will then be investigated. We also intend to determine the conformations, both in aqueous solution and bound to AMA1, of oligopeptides identified by phage display as binding to AMA1 and blocking its binding to red blood cells. The overall goals of this work are to determine the structure of AMA1 and to define the structural basis for its interaction with antibodies and small peptides that are capable of blocking its activity. This information will provide a molecular basis for the design of either synthetic antigens capable of eliciting a protective immune response against AMA1 or peptidomimetic inhibitors of AMA1. Either or both of these may be useful in the prevention or treatment of malaria.

Funding Amount $AUD 242,545.90

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant