PRODUCTION OF HUMAN ANTIMALARIAL CRISIS FORM FACTOR

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Malaria, due to Plasmodium falciparum remains the most important human infectious disease in the world. Past control measures have been inadequate to limit the incidence and consequences of the disease. Currently, a great deal of attention and funding is being directed to the search for an antimalarial vaccine. These programs support the search for parasite antigens which could stimulate protective immunity in humans via antibody-dependent mechanisms. However, the acquired protective immunity to malaria found in humans living in malarious areas is poorly understood. It is possible, if not likely, that vaccines based on antibody alone will be of relatively limited use in controlling malaria. Jensen et al reported strong evidence that naturally acquired immunity to falciparum malaria in Sudan involves a major contribution from cell-mediated immune responses. In vitro, Sudanese immune sera cause a profound retardation in the intraerythrocytic development of P. falciparum resulting in the appearance of morphologically typical "crisis forms." We have termed the factor responsible for the activity crisis-form factor (CFF). The long term objectives of this research are to be able to produce CFF for use as a possible therapeutic agent in the clinical management of malaria, or to stimulate production of protective substance in vivo as a potential means of prophylaxis. Both approaches require the purification, characterization and specific quantitation of CFF from human immune serum sources. The specific aim of the Phase 1 feasibility study is to develop immunoassay procedures based on the production of anti-CFF monoclonal antibodies.