Plasmepsin 4-deficient Plasmodium berghei are virulence attenuated and induce protective immunity against experimental malaria

Spaccapelo, R. et al. (2010) Plasmepsin 4-deficient Plasmodium berghei are virulence attenuated and induce protective immunity against experimental malaria. American Journal of Pathology, 176(1), pp. 205-217. (doi:10.2353/ajpath.2010.090504)

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Publisher's URL: http://dx.doi.org/10.2353/ajpath.2010.090504

Abstract

Plasmodium parasites lacking plasmepsin 4 (PM4), an aspartic protease that functions in the lysosomal compartment and contributes to hemoglobin digestion, have only a modest decrease in the asexual blood-stage growth rate; however, PM4 deficiency in the rodent malaria parasite Plasmodium berghei results in significantly less virulence than that for the parental parasite. P. berghei {Delta}pm4 parasites failed to induce experimental cerebral malaria (ECM) in ECM-susceptible mice, and ECM-resistant mice were able to clear infections. Furthermore, after a single infection, all convalescent mice were protected against subsequent parasite challenge for at least 1 year. Real-time in vivo parasite imaging and splenectomy experiments demonstrated that protective immunity acted through antibody-mediated parasite clearance in the spleen. This work demonstrates, for the first time, that a single Plasmodium gene disruption can generate virulence-attenuated parasites that do not induce cerebral complications and, moreover, are able to stimulate strong protective immunity against subsequent challenge with wild-type parasites. Parasite blood-stage attenuation should help identify protective immune responses against malaria, unravel parasite-derived factors involved in malarial pathologies, such as cerebral malaria, and potentially pave the way for blood-stage whole organism vaccines

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Waters, Professor Andy
Authors: Spaccapelo, R., Janse, C.J., Caterbi, S., Franke-Fayard, B., Bonilla, J. A., Syphard, L. M., Di Cristina, M., Dottorini, T., Savarino, A., Cassone, A., Bistoni, F., Waters, A.P., Dame, J. B., and Crisanti, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:American Journal of Pathology
Journal Abbr.:Am. J. Pathol.
Publisher:American Society for Investigative Pathology
ISSN:0002-9440
ISSN (Online):1525-2191
Published Online:29 November 2010

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