Studies on attenuated malaria parasites for the development of vaccine.

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It is widely known from field observation that malaria infections do not create strong protective immunity to reinfections. The fact casts a pessimistic shadow over the vaccine development against malaria. We have found that an attenuated mutant can produce much stronger immunity in terms of long lasting effect. Plasmodium (P) berghei XAT is an irradiation-induced attenuated variant of P. berghei NK65. The wild NK65 induces poor immunity in mice and causes 100% lethality in mice. While, P. berghei-XAT causes modest self-limiting infections in Balb/c mice and a single inoculation with the variant strain induces a long lasting immunity in mice against a challenge inoculation with the original virulent NK65 strain. Hence, combination experiments of NK65 and XAT parasites will be a good model to develop long lasting and effective vaccine studies. In this study, differences between the original NK65 strain and the derivative XAT were studied at the molecular level using monoclonal antibodies. Monoclonal antibodies to XAT strain were developed and one designated D3-1A12 was reactive only with XAT at the stage of schizont. The monoclonal antibody precipitated a molecule of 240 Kd from metabolically labeled parasite antigens derived from XAT. On the other hand, polyclonal antibodies to virulent NK65 and to attenuated XAT were prepared respectively. Western blot using each antibody showed that 30 Kd protein was defective in attenuated parasite. By O'Farrell's two dementional electrophoresis two distinctive polypeptide spots were detected. Reproducibility of X-ray irradiation attenuation were confirmed with P. yoelii nigeriensismice system.