Dr. Andrea Crisanti and colleagues have found that weakened Plasmodium elicits a protective immune response.
They report their data in the January 2010 issue of the American Journal Pathology.
Malaria is a mosquito-borne disease that each year affects from 300-500 million people. Malaria is caused by infection with Plasmodium parasites, which go through a number of life cycle changes inside the host, increasing the challenges of malarial vaccine development.
Plasmepsin 4 is a digestive enzyme that is critical for Plasmodium growth and survival within the host red blood cells. Spaccapelo et al therefore examined Plasmodium parasites that lacked plasmepsin 4 expression for deficiencies in parasite growth and virulence. Although there was only a modest effect of plasmepsin 4 deficiency on Plasmodium growth and development within red blood cells, plasmepsin 4-null parasites were significantly less virulent than their wild-type counterparts. Infection with plasmepsin 4-deficient parasites, in contrast to infection with wild-type Plasmodium, did not induce cerebral complications. Furthermore, plasmepsin 4-null Plasmodium induced strong protective immune responses against secondary immunization with wild-type Plasmodium. Virulence-attenuated Plasmodium may therefore provide a model for assessing genetically-attenuated malarial vaccine candidates.
Dr. Crisanti and colleagues conclude that "it is possible, by engineered inactivation of parasite proteins, to generate attenuated blood stage parasites that are capable of inducing protective immunity against blood-stage infection. Such parasites should be powerful tools in elucidating parasite-derived factors that cause severe disease and should provide additional insight into factors that are required to induce protective immunity."
- Spaccapelo R, Janse CJ, Caterbi S, Franke-Fayard B, Bonilla JA, Syphard LM, Di Cristina M, Dottorini T, Savarino A, Cassone A, Bistoni F, Waters AP, Dame JB, Crisanti A. Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental Malaria. American Journal Of Pathology, 2010; 176 (1): 205 DOI: 10.2353/ajpath.2010.090504
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