Chemical Attenuation of Plasmodium berghei Sporozoites Induces Sterile Immunity in Mice

Institute of Parasitology and Centre for Host-Parasite Interactions, McGill University, 21111 Lakeshore Road, Sainte-Anne-de-Bellevue, Quebec H9X3V9, Canada.
Infection and immunity (Impact Factor: 3.73). 04/2008; 76(3):1193-9. DOI: 10.1128/IAI.01399-07
Source: PubMed


Radiation and genetic attenuation of Plasmodium sporozoites are two approaches for whole-organism vaccines that protect against malaria. We evaluated chemical attenuation
of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent
centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits
Plasmodium falciparum growth in vitro. Here we show that treatment of Plasmodium berghei sporozoites with centanamycin impaired parasite function both in vitro and in vivo. The infection of hepatocytes by sporozoites
in vitro was significantly reduced, and treated parasites showed arrested liver stage development. Inoculation of mice with
sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and
C57BL/6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild-type sporozoites. Our
findings demonstrate that chemically attenuated sporozoites could be a viable alternative for the production of an effective
liver stage vaccine for malaria.

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    • "The lack of significant progress with subunit vaccines that contain only (parts of) single proteins, together with an enhanced understanding of the protective immunity to malaria has generated new interest in vaccines based on whole blood stage parasite49. Sporozoites that have been attenuated either by radiation or by genetic modification have shown promise as a whole parasite approach to pre-erythrocytic vaccination505152535455. Recent studies have demonstrated that the disruption of individual genes was not sufficient to completely attenuate parasite virulence. "
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