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Infection and Immunity, March 2008, p. 1200-1206, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.00566-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Class II-Restricted Protective Immunity Induced by Malaria Sporozoites

Giane A. Oliveira,^1, Kota Arun Kumar,² J. Mauricio Calvo-Calle,^1, Caroline Othoro,¹ David Altszuler,¹ Victor Nussenzweig,² and Elizabeth H. Nardin^1*

Department of Medical Parasitology,¹ Department of Pathology, Michael Hiedelberger Division of Immunology, New York University School of Medicine, New York, New York²

Received 18 April 2007/ Returned for modification 10 June 2007/ Accepted 17 December 2007

The irradiated-sporozoite vaccine elicits sterile immunity against Plasmodium parasites in experimental rodent hosts and human volunteers. Based on rodent malaria models, it has been proposed that CD8⁺ T cells are the key protective effector mechanism required in sporozoite-induced immunity. To investigate the role of class II-restricted immunity in protective immunity, we immunized β₂-microglobulin knockout (β₂M^–/–) mice with irradiated Plasmodium yoelii or P. berghei sporozoites. Sterile immunity was obtained in the CD8⁺-T-cell-deficient mice immunized with either P. berghei or P. yoelii sporozoites. β₂M^–/– mice with the BALB/c (H-2^d) genetic background as well as those with the C57BL (H-2^b) genetic background were protected. Effector mechanisms included CD4⁺ T cells, mediated in part through the production of gamma interferon, and neutralizing antibodies that targeted the extracellular sporozoites. We conclude that in the absence of class I-restricted CD8⁺ T cells, sporozoite-induced protective immunity can be effectively mediated by class II-restricted immune effector mechanisms. These results support efforts to develop subunit vaccines that effectively elicit high levels of antibody and CD4⁺ T cells to target Plasmodium preerythrocytic stages.

Published ahead of print on 26 December 2007.

Editor: J. F. Urban, Jr.

Present address: Regeneron Pharmaceuticals Inc., Old Saw Mill River Rd., Tarrytown, NY.

Present address: University of Massachusetts School of Medicine, Worcester, MA.