An alternative approach to malaria vaccine with a permanent attenuated mutant from a high virulence plasmodium berghei strain

Abstract

An alternative approach to malaria vaccine with the use of Plasmodium berghei NK65XAT (XAT) is reviewed. XAT is a permanent low virulence strain derived from high virulence P. berghei NK65 (NK65) by irradiation. Although one organism of parent NK65 could kill one mouse, as many as 10(7) XAT parasites caused modest self limiting parasitaemia in immuno-competent mice. In the mice recovered from XAT infection, long lasting immunity to challenge not only by parent NK65, but also by ANKA so far as different species of rodent Plasmodia was seen. The XAT parasites invaded selectively into immature erythrocytes. Because of this feature, the attenuated parasite might induce potent and long-lasting immunity presumably with the background of MHC antigen expression on infected cells. Immunopathologic reactions in mice infected with XAT were modest comparing to those seen in mice with parent NK65 infection. Attenuation was also tested using P. yoelii nigeriensis with which cyclical transmission with A. stephensi was established. Although similar attenuation occurred by X-ray irradiation, produced parasites eventually reverted to virulence after several animal passages. Irradiation was also attempted to induce attenuated P. falciparum mutant and a parasite of a slow multiplication feature was obtained in an experiment. We would propose an alternative approach in the study of malaria vaccine using attenuated live organisms which confers potent and long lasting immunity to the host.