Mouse monoclonal antibodies, mcAB, confer protection against rodent malaria sporozoites and blood stages, and recognize antigens that can induce protective immunity. Observations in man, that transfer of immunoglobulin from adults immune against P. falciparum, Pf, malaria can control potentially lethal infections in non-immune children, and that murine mcAB against Pf antigens can inhibit the growth of Pf in vitro, as well as advances in establishing human-human hybridomas, have led to this proposal. Our objectives are to produce human mcAB against Pf, and to establish the conditions that favor selection of hybridomas making IgG against Pf blood stage antigens, using these to isolate potentially protective Pf antigens. This includes the following approaches: (1) Production of hybridomas by fusion of B lympho-cytes from individuals immune against Pf and human neoplastic B lymphocyte lines; (2) determination of optimal conditions yielding IgG-producing hybridomas, by variation of (a) source of B lymphocytes, e.g. from peripheral blood or spleen, duration and techniques of in vitro stimulation of lymphocytes by mitogens, or Pf antigens and (b) use of different human B lymphoblastoid cells as fusion partners; (3) search by radioimmune assay, and by assays testing in vitro inhibition of parasite growth, for mcAB reactive with Pf blood stage antigens; (4) use of human mcAB to identify, isolate, and characterize immunogenic Pf antigens and characterize their relevant antigen epitopes; (5) search for autoantibodies against erythrocyte components.
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