Letter abstract
Nature Medicine 14, 954 - 958 (2008)
Published online: 31 August 2008 | doi:10.1038/nm.1867
Attenuated Plasmodium yoelii lacking purine nucleoside phosphorylase confer protective immunity
Li-Min Ting1, Mathieu Gissot1, Alida Coppi2, Photini Sinnis2 & Kami Kim1
Malaria continues to devastate sub-Saharan Africa owing to the emergence of drug resistance to established antimalarials and to the lack of an efficacious vaccine. Plasmodium species have a unique streamlined purine pathway in which the dual specificity enzyme purine nucleoside phosphorylase (PNP) functions in both purine recycling and purine salvage1, 2, 3, 4. To evaluate the importance of PNP in an in vivo model of malaria, we disrupted PyPNP, the gene encoding PNP in the lethal Plasmodium yoelii YM strain. P. yoelii parasites lacking PNP were attenuated and cleared in mice. Although able to form gametocytes, PNP-deficient parasites did not form oocysts in mosquito midguts and were not transmitted from mosquitoes to mice. Mice given PNP-deficient parasites were immune to subsequent challenge to a lethal inoculum of P. yoelii YM and to challenge from P. yoelii 17XNL, another strain. These in vivo studies with PNP-deficient parasites support purine salvage as a target for antimalarials. They also suggest a strategy for the development of attenuated nontransmissible metabolic mutants as blood-stage malaria vaccine strains.
- Departments of Medicine and Microbiology & Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
- Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, New York 10010, USA.
Correspondence to: Kami Kim1 e-mail: kkim@aecom.yu.edu
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