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Cutting Edge: A New Tool to Evaluate Human Pre-Erythrocytic Malaria Vaccines: Rodent Parasites Bearing a Hybrid Plasmodium falciparum Circumsporozoite Protein¹

Cathrine Persson^2,3,*, Giane A. Oliveira^2,, Ali A. Sultan^4,*, Purnima Bhanot^*, Victor Nussenzweig^* and Elizabeth Nardin^2,

^* Michael Heidelberger Division of Immunology, Department of Pathology, and Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10016

Malaria vaccines containing the Plasmodium falciparum Circumsporozoite protein repeat domain are undergoing human trials. There is no simple method to evaluate the effect of vaccine-induced responses on P. falciparum sporozoite infectivity. Unlike the rodent malaria Plasmodium berghei, P. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. We generated a recombinant P. berghei parasite bearing P. falciparum Circumsporozoite protein repeats. These hybrid sporozoites are fully infective in vivo and in vitro. Monoclonal and polyclonal Abs to P. falciparum repeats neutralize hybrid parasite infectivity, and mice immunized with a P. falciparum vaccine are protected against challenge with hybrid sporozoites.

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